Trial Outcomes & Findings for A Dose-escalating Clinical Trial With KH176 (NCT NCT02544217)
NCT ID: NCT02544217
Last Updated: 2021-10-18
Results Overview
Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
Post dose Day 7
Results posted on
2021-10-18
Participant Flow
All studies were conducted at the Drug Research Unit Ghent. Participants agreed to stay in the Drug Research Unit during the first 24 h after dosing (SAD) and during Day 8 (MAD).
Participant milestones
| Measure |
Single Ascending Group I
2 alternating groups receiving escalating single doses of active/placebo
KH176
placebo
|
Single Ascending Group II
2 alternating groups receiving escalating single doses of active/placebo
KH176
placebo
|
Multiple Ascending Group III
3 multiple escalating groups, receiving active/placebo
KH176
placebo
|
Multiple Ascending Group IV
3 multiple escalating groups, receiving active/placebo
KH176
placebo
|
Multiple Ascending Group V
3 multiple escalating groups, receiving active/placebo
KH176
placebo
|
Placebo
Group receiving placebo
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
7
|
7
|
4
|
4
|
4
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
4
|
4
|
4
|
6
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Single Ascending Group I
2 alternating groups receiving escalating single doses of active/placebo
KH176
placebo
|
Single Ascending Group II
2 alternating groups receiving escalating single doses of active/placebo
KH176
placebo
|
Multiple Ascending Group III
3 multiple escalating groups, receiving active/placebo
KH176
placebo
|
Multiple Ascending Group IV
3 multiple escalating groups, receiving active/placebo
KH176
placebo
|
Multiple Ascending Group V
3 multiple escalating groups, receiving active/placebo
KH176
placebo
|
Placebo
Group receiving placebo
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Dose-escalating Clinical Trial With KH176
Baseline characteristics by cohort
| Measure |
SAD Group I
n=7 Participants
SAD group I: 10mg, 100mg, 800mg
|
SAD Group II
n=7 Participants
SAD group II: 30mg, 300mg, 2000mg
|
MAD Group III
n=4 Participants
MAD group III:100mg bis in die (BID)
|
MAD Group IV
n=4 Participants
MAD group IV: 200mg BID
|
MAD Group V
n=4 Participants
MAD group V: 400mg BID
|
Placebo
n=6 Participants
Placebo group
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
30.4 years
STANDARD_DEVIATION 10.5 • n=93 Participants
|
32.0 years
STANDARD_DEVIATION 11.3 • n=4 Participants
|
40.8 years
STANDARD_DEVIATION 13.0 • n=27 Participants
|
34.5 years
STANDARD_DEVIATION 11.6 • n=483 Participants
|
44.0 years
STANDARD_DEVIATION 8.2 • n=36 Participants
|
44.7 years
STANDARD_DEVIATION 9.8 • n=10 Participants
|
40.0 years
STANDARD_DEVIATION 4.0 • n=115 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
6 Participants
n=10 Participants
|
32 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
5 Participants
n=10 Participants
|
29 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
6 Participants
n=10 Participants
|
32 Participants
n=115 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Region of Enrollment
Belgium
|
7 participants
n=93 Participants
|
7 participants
n=4 Participants
|
4 participants
n=27 Participants
|
4 participants
n=483 Participants
|
4 participants
n=36 Participants
|
6 participants
n=10 Participants
|
32 participants
n=115 Participants
|
|
Height
|
178.07 cm
STANDARD_DEVIATION 6.56 • n=93 Participants
|
176.01 cm
STANDARD_DEVIATION 8.11 • n=4 Participants
|
184.63 cm
STANDARD_DEVIATION 2.81 • n=27 Participants
|
181.75 cm
STANDARD_DEVIATION 5.25 • n=483 Participants
|
175.70 cm
STANDARD_DEVIATION 3.18 • n=36 Participants
|
175.55 cm
STANDARD_DEVIATION 8.25 • n=10 Participants
|
184.0 cm
STANDARD_DEVIATION 4.0 • n=115 Participants
|
|
Weight
|
82.86 kg
STANDARD_DEVIATION 10.56 • n=93 Participants
|
74.29 kg
STANDARD_DEVIATION 12.61 • n=4 Participants
|
89.05 kg
STANDARD_DEVIATION 11.84 • n=27 Participants
|
77.85 kg
STANDARD_DEVIATION 11.96 • n=483 Participants
|
81.10 kg
STANDARD_DEVIATION 4.82 • n=36 Participants
|
72.03 kg
STANDARD_DEVIATION 6.06 • n=10 Participants
|
80.0 kg
STANDARD_DEVIATION 8.0 • n=115 Participants
|
|
BMI
|
26.09 kg/m^2
STANDARD_DEVIATION 2.51 • n=93 Participants
|
24.01 kg/m^2
STANDARD_DEVIATION 4.01 • n=4 Participants
|
26.10 kg/m^2
STANDARD_DEVIATION 2.74 • n=27 Participants
|
23.60 kg/m^2
STANDARD_DEVIATION 3.82 • n=483 Participants
|
26.28 kg/m^2
STANDARD_DEVIATION 1.67 • n=36 Participants
|
23.43 kg/m^2
STANDARD_DEVIATION 1.98 • n=10 Participants
|
24.0 kg/m^2
STANDARD_DEVIATION 4.0 • n=115 Participants
|
PRIMARY outcome
Timeframe: Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow upPopulation: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Baseline (Pre-dose Day 1)
|
386.2 msec
Standard Deviation 17.2
|
395.0 msec
Standard Deviation 9.8
|
385.8 msec
Standard Deviation 14.8
|
399.3 msec
Standard Deviation 8.3
|
390.3 msec
Standard Deviation 14.6
|
393.5 msec
Standard Deviation 14.2
|
386.5 msec
Standard Deviation 10.9
|
385.3 msec
Standard Deviation 16.8
|
369.0 msec
Standard Deviation 14.1
|
386.5 msec
Standard Deviation 13.2
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Change from baseline (BL)at 1h
|
4.0 msec
Standard Deviation 2.8
|
-2.0 msec
Standard Deviation 8.7
|
-0.3 msec
Standard Deviation 3.8
|
-3.5 msec
Standard Deviation 6.0
|
0.8 msec
Standard Deviation 4.0
|
0.8 msec
Standard Deviation 5.7
|
0.3 msec
Standard Deviation 7.6
|
28.8 msec
Standard Deviation 19.0
|
4.5 msec
Standard Deviation 19.1
|
5.8 msec
Standard Deviation 2.6
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Change from BL at 2h
|
0.5 msec
Standard Deviation 7.9
|
-4.0 msec
Standard Deviation 6.6
|
-1.8 msec
Standard Deviation 7.9
|
-4.8 msec
Standard Deviation 6.1
|
-4.8 msec
Standard Deviation 3.0
|
1.5 msec
Standard Deviation 6.0
|
7.8 msec
Standard Deviation 10.0
|
28.5 msec
Standard Deviation 14.1
|
2.5 msec
Standard Deviation 13.4
|
1.8 msec
Standard Deviation 5.3
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Change from BL at 4h
|
6.5 msec
Standard Deviation 9.4
|
-2.2 msec
Standard Deviation 11.4
|
-3.8 msec
Standard Deviation 3.3
|
-4.3 msec
Standard Deviation 6.2
|
1.0 msec
Standard Deviation 5.7
|
3.8 msec
Standard Deviation 12.3
|
3.3 msec
Standard Deviation 7.2
|
26.0 msec
Standard Deviation 8.7
|
8.5 msec
Standard Deviation 17.7
|
0.3 msec
Standard Deviation 3.9
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Change from BL at 6h
|
6.2 msec
Standard Deviation 3.6
|
-2.7 msec
Standard Deviation 6.0
|
4.3 msec
Standard Deviation 6.3
|
-4.0 msec
Standard Deviation 7.3
|
-1.0 msec
Standard Deviation 8.3
|
5.8 msec
Standard Deviation 8.1
|
5.5 msec
Standard Deviation 2.5
|
26.0 msec
Standard Deviation 7.9
|
8.5 msec
Standard Deviation 12.0
|
6.0 msec
Standard Deviation 5.0
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Change from BL at 8h
|
-0.8 msec
Standard Deviation 7.3
|
-7.2 msec
Standard Deviation 4.0
|
-5.5 msec
Standard Deviation 7.4
|
-1.8 msec
Standard Deviation 9.2
|
4.3 msec
Standard Deviation 10.3
|
-1.8 msec
Standard Deviation 9.0
|
0.8 msec
Standard Deviation 7.5
|
23.3 msec
Standard Deviation 12.3
|
-2.5 msec
Standard Deviation 13.4
|
0.5 msec
Standard Deviation 5.4
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Change from BL at 12h
|
1.8 msec
Standard Deviation 6.7
|
-5.2 msec
Standard Deviation 4.8
|
-1.8 msec
Standard Deviation 2.6
|
-7.3 msec
Standard Deviation 6.8
|
0.0 msec
Standard Deviation 4.7
|
0.0 msec
Standard Deviation 8.0
|
8.0 msec
Standard Deviation 0.8
|
19.3 msec
Standard Deviation 11.1
|
5.5 msec
Standard Deviation 7.8
|
3.3 msec
Standard Deviation 6.2
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Change from BL at 24h
|
5.3 msec
Standard Deviation 12.4
|
-7.5 msec
Standard Deviation 9.3
|
-4.0 msec
Standard Deviation 7.3
|
-4.8 msec
Standard Deviation 5.6
|
0.3 msec
Standard Deviation 6.2
|
-4.3 msec
Standard Deviation 6.5
|
0.3 msec
Standard Deviation 9.7
|
11.3 msec
Standard Deviation 4.7
|
-1.0 msec
Standard Deviation 8.5
|
-3.8 msec
Standard Deviation 4.0
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF)
Change from BL at FU
|
-0.3 msec
Standard Deviation 12.4
|
2.8 msec
Standard Deviation 7.9
|
-1.3 msec
Standard Deviation 10.8
|
2.8 msec
Standard Deviation 8.0
|
2.8 msec
Standard Deviation 13.1
|
5.0 msec
Standard Deviation 6.1
|
-5.0 msec
Standard Deviation 3.2
|
3.3 msec
Standard Deviation 7.6
|
5.5 msec
Standard Deviation 10.6
|
6.5 msec
Standard Deviation 13.0
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1, day 7Population: Per protocol set
Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Pharmacodynamics of KH176
Ox glutathione (GSH)/Red Glutathati(GSSG) Day 1-0h
|
872 ratio GSH/GSSG
Standard Deviation 532
|
2083 ratio GSH/GSSG
Standard Deviation 674
|
2275 ratio GSH/GSSG
Standard Deviation 792
|
1584 ratio GSH/GSSG
Standard Deviation 491
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacodynamics of KH176
GSH/GSSG Day 7-0h
|
919 ratio GSH/GSSG
Standard Deviation 196
|
1923 ratio GSH/GSSG
Standard Deviation 433
|
1918 ratio GSH/GSSG
Standard Deviation 1007
|
1694 ratio GSH/GSSG
Standard Deviation 572
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacodynamics of KH176
GSH/GSSG Day 7-3h
|
779 ratio GSH/GSSG
Standard Deviation 87
|
2045 ratio GSH/GSSG
Standard Deviation 338
|
1935 ratio GSH/GSSG
Standard Deviation 699
|
1712 ratio GSH/GSSG
Standard Deviation 465
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacodynamics of KH176
GSH/GSSG Day 7-6h
|
1040 ratio GSH/GSSG
Standard Deviation 335
|
2113 ratio GSH/GSSG
Standard Deviation 687
|
1993 ratio GSH/GSSG
Standard Deviation 863
|
1718 ratio GSH/GSSG
Standard Deviation 542
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Pharmacodynamics of KH176
GSH/GSSG Day 7-12h
|
1361 ratio GSH/GSSG
Standard Deviation 606
|
1893 ratio GSH/GSSG
Standard Deviation 279
|
1875 ratio GSH/GSSG
Standard Deviation 697
|
1680 ratio GSH/GSSG
Standard Deviation 657
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 4 monthsPopulation: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
n=4 Participants
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
n=4 Participants
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
n=4 Participants
400mg BID/Day (over 7 days)
|
Placebo
n=6 Participants
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
TEAE
|
5 TEAE
|
2 TEAE
|
2 TEAE
|
5 TEAE
|
7 TEAE
|
1 TEAE
|
0 TEAE
|
28 TEAE
|
1 TEAE
|
1 TEAE
|
9 TEAE
|
6 TEAE
|
14 TEAE
|
17 TEAE
|
|
Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
Serious TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
|
Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
Not related TEAE
|
4 TEAE
|
0 TEAE
|
0 TEAE
|
2 TEAE
|
6 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
1 TEAE
|
1 TEAE
|
1 TEAE
|
1 TEAE
|
3 TEAE
|
3 TEAE
|
|
Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
Unlikely related
|
0 TEAE
|
2 TEAE
|
2 TEAE
|
3 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
1 TEAE
|
1 TEAE
|
2 TEAE
|
1 TEAE
|
|
Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
Possibly related
|
1 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
1 TEAE
|
0 TEAE
|
0 TEAE
|
3 TEAE
|
0 TEAE
|
0 TEAE
|
7 TEAE
|
4 TEAE
|
9 TEAE
|
13 TEAE
|
|
Relationship to Study Drug and Severity of Treatment-emergent Adverse Events
Related
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
1 TEAE
|
0 TEAE
|
25 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
0 TEAE
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group
Baseline (pre-dose Day 1)
|
4.947 cells 10^6/µL
Standard Deviation 0.488
|
4.933 cells 10^6/µL
Standard Deviation 0.307
|
4.793 cells 10^6/µL
Standard Deviation 0.455
|
5.030 cells 10^6/µL
Standard Deviation 0.458
|
4.953 cells 10^6/µL
Standard Deviation 0.247
|
5.137 cells 10^6/µL
Standard Deviation 0.393
|
4.973 cells 10^6/µL
Standard Deviation 0.141
|
4.623 cells 10^6/µL
Standard Deviation 0.395
|
5.095 cells 10^6/µL
Standard Deviation 0.120
|
4.985 cells 10^6/µL
Standard Deviation 0.343
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group
Change from BL at 24h
|
0.200 cells 10^6/µL
Standard Deviation 0.495
|
0.095 cells 10^6/µL
Standard Deviation 0.260
|
0.063 cells 10^6/µL
Standard Deviation 0.085
|
0.188 cells 10^6/µL
Standard Deviation 0.153
|
0.170 cells 10^6/µL
Standard Deviation 0.250
|
0.065 cells 10^6/µL
Standard Deviation 0.197
|
0.173 cells 10^6/µL
Standard Deviation 0.200
|
0.325 cells 10^6/µL
Standard Deviation 0.185
|
0.185 cells 10^6/µL
Standard Deviation 0.064
|
0.115 cells 10^6/µL
Standard Deviation 0.208
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group
Change from BL at FU
|
0.003 cells 10^6/µL
Standard Deviation 0.215
|
-0.013 cells 10^6/µL
Standard Deviation 0.149
|
0.185 cells 10^6/µL
Standard Deviation 0.104
|
-0.052 cells 10^6/µL
Standard Deviation 0.183
|
0.083 cells 10^6/µL
Standard Deviation 0.127
|
-0.147 cells 10^6/µL
Standard Deviation 0.041
|
-0.053 cells 10^6/µL
Standard Deviation 0.209
|
0.125 cells 10^6/µL
Standard Deviation 0.182
|
-0.150 cells 10^6/µL
Standard Deviation 0.339
|
0.050 cells 10^6/µL
Standard Deviation 0.211
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)
Baseline
|
2.3 mm/hr
Standard Deviation 1.4
|
2.8 mm/hr
Standard Deviation 2.1
|
1.3 mm/hr
Standard Deviation 0.5
|
1.8 mm/hr
Standard Deviation 1.0
|
2.0 mm/hr
Standard Deviation 1.4
|
3.0 mm/hr
Standard Deviation 4.0
|
7.3 mm/hr
Standard Deviation 8.5
|
4.0 mm/hr
Standard Deviation 3.2
|
5.0 mm/hr
Standard Deviation 2.8
|
2.5 mm/hr
Standard Deviation 3.0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)
Change from BL at 24h
|
0.5 mm/hr
Standard Deviation 0.5
|
0.3 mm/hr
Standard Deviation 1.0
|
0.0 mm/hr
Standard Deviation 0.0
|
1.0 mm/hr
Standard Deviation 0.8
|
0.0 mm/hr
Standard Deviation 0.8
|
0.3 mm/hr
Standard Deviation 1.0
|
0.3 mm/hr
Standard Deviation 0.6
|
3.0 mm/hr
Standard Deviation 3.6
|
-0.5 mm/hr
Standard Deviation 0.7
|
1.0 mm/hr
Standard Deviation 2.0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group)
Change from BL at FU
|
0.3 mm/hr
Standard Deviation 1.2
|
0.3 mm/hr
Standard Deviation 1.5
|
0.8 mm/hr
Standard Deviation 1.0
|
0.5 mm/hr
Standard Deviation 1.7
|
0.5 mm/hr
Standard Deviation 1.7
|
0.0 mm/hr
Standard Deviation 0.0
|
-2.3 mm/hr
Standard Deviation 6.8
|
0.5 mm/hr
Standard Deviation 1.0
|
0.0 mm/hr
Standard Deviation 0.0
|
0.0 mm/hr
Standard Deviation 0.0
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group
Change from BL at Day 8
|
4.8 mm/hr
Standard Deviation 5.7
|
0.8 mm/hr
Standard Deviation 2.2
|
2.5 mm/hr
Standard Deviation 1.7
|
0.3 mm/hr
Standard Deviation 1.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group
Baseline (pre-dose Day 1)
|
4.0 mm/hr
Standard Deviation 2.4
|
3.0 mm/hr
Standard Deviation 1.8
|
2.0 mm/hr
Standard Deviation 1.4
|
2.7 mm/hr
Standard Deviation 1.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group
Change from BL at Day 3
|
2.0 mm/hr
Standard Deviation 3.5
|
0.8 mm/hr
Standard Deviation 0.5
|
0.5 mm/hr
Standard Deviation 0.6
|
0.8 mm/hr
Standard Deviation 1.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group
Change from BL at FU
|
5.0 mm/hr
Standard Deviation 8.2
|
1.3 mm/hr
Standard Deviation 1.3
|
1.0 mm/hr
Standard Deviation 0.8
|
2.2 mm/hr
Standard Deviation 3.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group
Baseline (pre-dose Day 1)
|
43.77 %red cells to the volume of whole blood.
Standard Deviation 3.35
|
43.13 %red cells to the volume of whole blood.
Standard Deviation 2.79
|
43.10 %red cells to the volume of whole blood.
Standard Deviation 3.46
|
44.38 %red cells to the volume of whole blood.
Standard Deviation 3.28
|
42.98 %red cells to the volume of whole blood.
Standard Deviation 1.41
|
44.35 %red cells to the volume of whole blood.
Standard Deviation 2.88
|
44.05 %red cells to the volume of whole blood.
Standard Deviation 3.17
|
41.35 %red cells to the volume of whole blood.
Standard Deviation 1.68
|
44.35 %red cells to the volume of whole blood.
Standard Deviation 2.33
|
42.53 %red cells to the volume of whole blood.
Standard Deviation 1.50
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group
Change from BL at 24h
|
0.53 %red cells to the volume of whole blood.
Standard Deviation 1.28
|
0.60 %red cells to the volume of whole blood.
Standard Deviation 2.10
|
0.75 %red cells to the volume of whole blood.
Standard Deviation 0.91
|
1.95 %red cells to the volume of whole blood.
Standard Deviation 1.41
|
1.42 %red cells to the volume of whole blood.
Standard Deviation 2.12
|
1.03 %red cells to the volume of whole blood.
Standard Deviation 2.11
|
1.33 %red cells to the volume of whole blood.
Standard Deviation 1.80
|
2.33 %red cells to the volume of whole blood.
Standard Deviation 1.87
|
1.90 %red cells to the volume of whole blood.
Standard Deviation 0.28
|
0.68 %red cells to the volume of whole blood.
Standard Deviation 1.92
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group
Change from BL at FU
|
-0.43 %red cells to the volume of whole blood.
Standard Deviation 1.70
|
-0.65 %red cells to the volume of whole blood.
Standard Deviation 1.37
|
0.85 %red cells to the volume of whole blood.
Standard Deviation 1.45
|
-0.93 %red cells to the volume of whole blood.
Standard Deviation 1.91
|
0.10 %red cells to the volume of whole blood.
Standard Deviation 1.66
|
-2.02 %red cells to the volume of whole blood.
Standard Deviation 0.54
|
-1.15 %red cells to the volume of whole blood.
Standard Deviation 2.17
|
0.07 %red cells to the volume of whole blood.
Standard Deviation 1.41
|
-0.65 %red cells to the volume of whole blood.
Standard Deviation 3.04
|
0.55 %red cells to the volume of whole blood.
Standard Deviation 2.20
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD
Baseline (pre-dose Day 1)
|
30.32 pg/cell
Standard Deviation 1.83
|
29.70 pg/cell
Standard Deviation 0.98
|
30.78 pg/cell
Standard Deviation 1.71
|
30.38 pg/cell
Standard Deviation 0.49
|
30.00 pg/cell
Standard Deviation 1.75
|
29.63 pg/cell
Standard Deviation 0.68
|
30.28 pg/cell
Standard Deviation 1.26
|
29.80 pg/cell
Standard Deviation 1.16
|
30.25 pg/cell
Standard Deviation 1.77
|
29.65 pg/cell
Standard Deviation 2.13
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD
Change from BL at 24h - Day 1
|
0.08 pg/cell
Standard Deviation 0.34
|
0.23 pg/cell
Standard Deviation 0.59
|
0.17 pg/cell
Standard Deviation 0.26
|
-0.08 pg/cell
Standard Deviation 0.26
|
-0.15 pg/cell
Standard Deviation 0.13
|
-0.60 pg/cell
Standard Deviation 0.80
|
-0.25 pg/cell
Standard Deviation 0.37
|
0.33 pg/cell
Standard Deviation 0.41
|
0.25 pg/cell
Standard Deviation 0.64
|
0.20 pg/cell
Standard Deviation 0.34
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD
Change from BL at FU
|
-0.22 pg/cell
Standard Deviation 0.15
|
0.05 pg/cell
Standard Deviation 0.46
|
-0.28 pg/cell
Standard Deviation 0.57
|
-0.23 pg/cell
Standard Deviation 0.51
|
-0.42 pg/cell
Standard Deviation 0.37
|
-0.28 pg/cell
Standard Deviation 0.21
|
-0.58 pg/cell
Standard Deviation 0.22
|
0.12 pg/cell
Standard Deviation 0.39
|
-0.15 pg/cell
Standard Deviation 0.35
|
-0.08 pg/cell
Standard Deviation 0.15
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD
Baseline (pre-dose Day 1)
|
34.15 g/dL RBC
Standard Deviation 0.34
|
33.98 g/dL RBC
Standard Deviation 1.01
|
34.18 g/dL RBC
Standard Deviation 0.46
|
34.38 g/dL RBC
Standard Deviation 0.84
|
34.53 g/dL RBC
Standard Deviation 0.45
|
34.33 g/dL RBC
Standard Deviation 1.07
|
34.20 g/dL RBC
Standard Deviation 0.65
|
33.25 g/dL RBC
Standard Deviation 0.71
|
34.70 g/dL RBC
Standard Deviation 0.57
|
34.68 g/dL RBC
Standard Deviation 0.99
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD
Change from BL at 24h - Day 1
|
-0.07 g/dL RBC
Standard Deviation 0.32
|
0.43 g/dL RBC
Standard Deviation 0.42
|
0.00 g/dL RBC
Standard Deviation 0.35
|
-0.27 g/dL RBC
Standard Deviation 0.39
|
-0.17 g/dL RBC
Standard Deviation 0.15
|
-1.05 g/dL RBC
Standard Deviation 0.87
|
-0.20 g/dL RBC
Standard Deviation 0.42
|
0.82 g/dL RBC
Standard Deviation 0.29
|
0.10 g/dL RBC
Standard Deviation 0.57
|
0.45 g/dL RBC
Standard Deviation 0.68
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD
Change from BL at FU
|
0.17 g/dL RBC
Standard Deviation 0.62
|
0.47 g/dL RBC
Standard Deviation 0.42
|
0.27 g/dL RBC
Standard Deviation 0.54
|
0.18 g/dL RBC
Standard Deviation 0.60
|
-0.05 g/dL RBC
Standard Deviation 0.64
|
0.30 g/dL RBC
Standard Deviation 0.48
|
-0.13 g/dL RBC
Standard Deviation 0.61
|
1.00 g/dL RBC
Standard Deviation 0.12
|
-0.60 g/dL RBC
Standard Deviation 0.28
|
-0.20 g/dL RBC
Standard Deviation 0.42
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD
Change from BL at FU
|
-1.10 fL
Standard Deviation 1.85
|
-1.03 fL
Standard Deviation 0.46
|
-1.68 fL
Standard Deviation 0.90
|
-0.92 fL
Standard Deviation 1.28
|
-1.25 fL
Standard Deviation 1.54
|
-1.52 fL
Standard Deviation 0.69
|
-1.45 fL
Standard Deviation 1.02
|
-2.30 fL
Standard Deviation 1.00
|
1.10 fL
Standard Deviation 0.28
|
0.20 fL
Standard Deviation 0.81
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD
Change from BL at 24h
|
0.45 fL
Standard Deviation 0.85
|
-0.38 fL
Standard Deviation 1.09
|
0.35 fL
Standard Deviation 0.37
|
0.48 fL
Standard Deviation 0.41
|
0.00 fL
Standard Deviation 0.08
|
0.85 fL
Standard Deviation 0.73
|
-0.27 fL
Standard Deviation 0.21
|
-1.33 fL
Standard Deviation 0.72
|
0.60 fL
Standard Deviation 0.28
|
-0.55 fL
Standard Deviation 0.79
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD
Baseline (pre-dose Day 1)
|
88.75 fL
Standard Deviation 5.36
|
87.52 fL
Standard Deviation 3.71
|
90.15 fL
Standard Deviation 5.73
|
88.35 fL
Standard Deviation 2.88
|
86.93 fL
Standard Deviation 4.75
|
86.42 fL
Standard Deviation 2.83
|
88.55 fL
Standard Deviation 4.57
|
89.73 fL
Standard Deviation 4.24
|
87.10 fL
Standard Deviation 6.65
|
85.48 fL
Standard Deviation 4.36
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL at 2h - Day 1
|
0.5 msec
Standard Deviation 7.5
|
5.5 msec
Standard Deviation 8.1
|
7.3 msec
Standard Deviation 7.0
|
1.7 msec
Standard Deviation 5.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL at pre-dose Day 2
|
-4.3 msec
Standard Deviation 6.6
|
0.5 msec
Standard Deviation 5.7
|
3.3 msec
Standard Deviation 13.6
|
-4.8 msec
Standard Deviation 3.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Baseline (Pre-dose Day 1)
|
397.3 msec
Standard Deviation 18.4
|
384.3 msec
Standard Deviation 21.7
|
388.5 msec
Standard Deviation 4.7
|
393.0 msec
Standard Deviation 18.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL Day 7 at 12h - Day 7
|
-4.3 msec
Standard Deviation 4.6
|
-5.0 msec
Standard Deviation 3.5
|
-10.0 msec
Standard Deviation 4.7
|
1.7 msec
Standard Deviation 6.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL at 24h - Day 1
|
-4.3 msec
Standard Deviation 6.6
|
0.5 msec
Standard Deviation 5.7
|
3.3 msec
Standard Deviation 13.6
|
-4.8 msec
Standard Deviation 3.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL Day 7 at 1h - Day 7
|
-1.3 msec
Standard Deviation 10.2
|
-3.0 msec
Standard Deviation 3.3
|
-6.5 msec
Standard Deviation 8.1
|
-2.2 msec
Standard Deviation 2.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL Day 7 at 2h - Day 7
|
-3.5 msec
Standard Deviation 2.5
|
-0.3 msec
Standard Deviation 8.2
|
-0.8 msec
Standard Deviation 3.2
|
-0.3 msec
Standard Deviation 10.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL Day 7 at 4h
|
-7.5 msec
Standard Deviation 4.7
|
-3.8 msec
Standard Deviation 3.5
|
-5.8 msec
Standard Deviation 7.7
|
3.0 msec
Standard Deviation 11.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL Day 7 BL at 6h - Day 7
|
-1.8 msec
Standard Deviation 7.3
|
2.0 msec
Standard Deviation 4.7
|
-7.3 msec
Standard Deviation 1.9
|
-0.5 msec
Standard Deviation 21.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL Day 7 at 8h - Day 7
|
-11.3 msec
Standard Deviation 3.2
|
-3.8 msec
Standard Deviation 6.9
|
-11.0 msec
Standard Deviation 5.3
|
0.8 msec
Standard Deviation 3.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL at pre-dose Day 3
|
0.5 msec
Standard Deviation 8.6
|
2.8 msec
Standard Deviation 6.4
|
10.5 msec
Standard Deviation 17.2
|
-7.5 msec
Standard Deviation 6.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL at pre-dose Day 4
|
2.5 msec
Standard Deviation 14.6
|
0.5 msec
Standard Deviation 13.6
|
7.3 msec
Standard Deviation 10.2
|
-6.7 msec
Standard Deviation 8.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL at pre-dose Day 5
|
6.0 msec
Standard Deviation 13.3
|
2.5 msec
Standard Deviation 7.2
|
10.8 msec
Standard Deviation 6.7
|
-5.3 msec
Standard Deviation 7.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL at pre-dose Day 6
|
-1.3 msec
Standard Deviation 12.5
|
-1.5 msec
Standard Deviation 6.2
|
7.8 msec
Standard Deviation 8.0
|
-8.2 msec
Standard Deviation 11.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL at pre-dose Day 7
|
-1.0 msec
Standard Deviation 11.9
|
3.0 msec
Standard Deviation 9.5
|
13.5 msec
Standard Deviation 8.7
|
-8.8 msec
Standard Deviation 9.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QTcF
Change from BL at FU
|
-2.3 msec
Standard Deviation 5.0
|
4.0 msec
Standard Deviation 6.3
|
-0.5 msec
Standard Deviation 14.4
|
6.7 msec
Standard Deviation 14.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group
Baseline (pre-dose Day 1)
|
4.435 cells 10^3/µL
Standard Deviation 0.526
|
4.773 cells 10^3/µL
Standard Deviation 0.548
|
4.313 cells 10^3/µL
Standard Deviation 0.418
|
4.863 cells 10^3/µL
Standard Deviation 0.372
|
4.395 cells 10^3/µL
Standard Deviation 0.694
|
4.475 cells 10^3/µL
Standard Deviation 0.733
|
4.853 cells 10^3/µL
Standard Deviation 0.372
|
5.118 cells 10^3/µL
Standard Deviation 0.647
|
5.815 cells 10^3/µL
Standard Deviation 2.072
|
5.535 cells 10^3/µL
Standard Deviation 1.467
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group
Change from BL at 24h
|
0.343 cells 10^3/µL
Standard Deviation 0.525
|
-0.057 cells 10^3/µL
Standard Deviation 0.359
|
-0.033 cells 10^3/µL
Standard Deviation 0.317
|
0.160 cells 10^3/µL
Standard Deviation 0.329
|
0.257 cells 10^3/µL
Standard Deviation 0.529
|
0.160 cells 10^3/µL
Standard Deviation 0.753
|
0.528 cells 10^3/µL
Standard Deviation 0.324
|
0.655 cells 10^3/µL
Standard Deviation 0.666
|
0.220 cells 10^3/µL
Standard Deviation 0.721
|
-0.280 cells 10^3/µL
Standard Deviation 0.555
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group
Change from BL at FU
|
0.258 cells 10^3/µL
Standard Deviation 0.309
|
-0.203 cells 10^3/µL
Standard Deviation 0.662
|
0.288 cells 10^3/µL
Standard Deviation 0.211
|
-0.073 cells 10^3/µL
Standard Deviation 0.367
|
0.395 cells 10^3/µL
Standard Deviation 0.617
|
-0.287 cells 10^3/µL
Standard Deviation 0.618
|
0.215 cells 10^3/µL
Standard Deviation 0.266
|
-0.320 cells 10^3/µL
Standard Deviation 0.592
|
-0.560 cells 10^3/µL
Standard Deviation 1.202
|
-0.745 cells 10^3/µL
Standard Deviation 1.535
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group
Change from BL at 24h
|
-13.3 cells/µL
Standard Deviation 223.4
|
-16.7 cells/µL
Standard Deviation 347.3
|
-45.0 cells/µL
Standard Deviation 192.8
|
-172.5 cells/µL
Standard Deviation 227.1
|
-27.5 cells/µL
Standard Deviation 58.0
|
92.5 cells/µL
Standard Deviation 225.6
|
287.5 cells/µL
Standard Deviation 353.7
|
37.5 cells/µL
Standard Deviation 159.9
|
-135.0 cells/µL
Standard Deviation 261.6
|
-70.0 cells/µL
Standard Deviation 177.6
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group
Baseline (pre-dose Day 1)
|
1570.0 cells/µL
Standard Deviation 227.0
|
1748.3 cells/µL
Standard Deviation 441.1
|
1655.0 cells/µL
Standard Deviation 200.4
|
1862.5 cells/µL
Standard Deviation 548.2
|
1485.0 cells/µL
Standard Deviation 169.2
|
1570.0 cells/µL
Standard Deviation 273.1
|
1550.0 cells/µL
Standard Deviation 275.3
|
1497.5 cells/µL
Standard Deviation 707.6
|
2260.0 cells/µL
Standard Deviation 975.8
|
1640.0 cells/µL
Standard Deviation 243.2
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group
Change from BL at FU
|
86.7 cells/µL
Standard Deviation 265.3
|
-45.0 cells/µL
Standard Deviation 253.3
|
180.0 cells/µL
Standard Deviation 186.5
|
-92.5 cells/µL
Standard Deviation 315.7
|
127.5 cells/µL
Standard Deviation 425.2
|
-32.5 cells/µL
Standard Deviation 174.6
|
135.0 cells/µL
Standard Deviation 294.2
|
-7.5 cells/µL
Standard Deviation 244.0
|
-190.0 cells/µL
Standard Deviation 410.1
|
-27.5 cells/µL
Standard Deviation 125.8
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group
Change from BL at FU
|
205.0 cells/µL
Standard Deviation 161.8
|
-16.7 cells/µL
Standard Deviation 335.4
|
90.0 cells/µL
Standard Deviation 183.5
|
107.5 cells/µL
Standard Deviation 252.1
|
255.0 cells/µL
Standard Deviation 519.0
|
-167.5 cells/µL
Standard Deviation 480.7
|
-12.5 cells/µL
Standard Deviation 203.5
|
-382.5 cells/µL
Standard Deviation 232.9
|
-205.0 cells/µL
Standard Deviation 445.5
|
-557.5 cells/µL
Standard Deviation 1326.2
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group
Change from BL at 24h
|
356.7 cells/µL
Standard Deviation 336.9
|
98.3 cells/µL
Standard Deviation 171.2
|
7.5 cells/µL
Standard Deviation 196.7
|
410.0 cells/µL
Standard Deviation 593.0
|
272.5 cells/µL
Standard Deviation 419.1
|
165.0 cells/µL
Standard Deviation 335.5
|
285.0 cells/µL
Standard Deviation 155.0
|
440.0 cells/µL
Standard Deviation 601.5
|
445.0 cells/µL
Standard Deviation 459.6
|
-122.5 cells/µL
Standard Deviation 584.3
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group
Baseline (pre-dose Day 1)
|
2276.7 cells/µL
Standard Deviation 551.2
|
2296.7 cells/µL
Standard Deviation 658.7
|
2117.5 cells/µL
Standard Deviation 369.2
|
2365.0 cells/µL
Standard Deviation 820.8
|
2380.0 cells/µL
Standard Deviation 679.0
|
2197.5 cells/µL
Standard Deviation 835.9
|
2565.0 cells/µL
Standard Deviation 462.6
|
2360.0 cells/µL
Standard Deviation 438.1
|
2280.0 cells/µL
Standard Deviation 169.7
|
3192.5 cells/µL
Standard Deviation 1523.9
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group
Baseline
|
39.93 % of red cells to volume of whole blood.
Standard Deviation 1.20
|
43.40 % of red cells to volume of whole blood.
Standard Deviation 3.51
|
45.10 % of red cells to volume of whole blood.
Standard Deviation 1.33
|
43.30 % of red cells to volume of whole blood.
Standard Deviation 1.95
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group
Change from BL at FU
|
0.92 % of red cells to volume of whole blood.
Standard Deviation 1.06
|
-0.10 % of red cells to volume of whole blood.
Standard Deviation 3.26
|
-1.05 % of red cells to volume of whole blood.
Standard Deviation 0.64
|
-0.75 % of red cells to volume of whole blood.
Standard Deviation 2.32
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group
Change from BL at Day 3
|
2.67 % of red cells to volume of whole blood.
Standard Deviation 1.94
|
1.17 % of red cells to volume of whole blood.
Standard Deviation 1.69
|
0.13 % of red cells to volume of whole blood.
Standard Deviation 0.45
|
1.70 % of red cells to volume of whole blood.
Standard Deviation 1.91
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group
Change from BL at Day 8
|
3.30 % of red cells to volume of whole blood.
Standard Deviation 1.24
|
1.22 % of red cells to volume of whole blood.
Standard Deviation 3.26
|
0.10 % of red cells to volume of whole blood.
Standard Deviation 1.22
|
1.93 % of red cells to volume of whole blood.
Standard Deviation 2.69
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group
Baseline (pre-dose Day 1)
|
115.0 cells/µL
Standard Deviation 50.1
|
191.7 cells/µL
Standard Deviation 109.4
|
110.0 cells/µL
Standard Deviation 49.7
|
137.5 cells/µL
Standard Deviation 83.4
|
112.5 cells/µL
Standard Deviation 36.9
|
200.0 cells/µL
Standard Deviation 78.7
|
245.0 cells/µL
Standard Deviation 233.6
|
110.0 cells/µL
Standard Deviation 71.6
|
650.0 cells/µL
Standard Deviation 792.0
|
152.5 cells/µL
Standard Deviation 81.0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group
Change from BL at 24h
|
-5.0 cells/µL
Standard Deviation 16.4
|
-50.0 cells/µL
Standard Deviation 40.5
|
-17.5 cells/µL
Standard Deviation 9.6
|
-22.5 cells/µL
Standard Deviation 42.7
|
-15.0 cells/µL
Standard Deviation 12.9
|
-37.5 cells/µL
Standard Deviation 47.9
|
-25.0 cells/µL
Standard Deviation 33.2
|
-25.0 cells/µL
Standard Deviation 26.5
|
-25.0 cells/µL
Standard Deviation 7.1
|
-30.0 cells/µL
Standard Deviation 47.6
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group
Change from BL at FU
|
-13.3 cells/µL
Standard Deviation 16.3
|
-58.3 cells/µL
Standard Deviation 93.5
|
-17.5 cells/µL
Standard Deviation 25.0
|
-12.5 cells/µL
Standard Deviation 43.5
|
-2.5 cells/µL
Standard Deviation 18.9
|
-42.5 cells/µL
Standard Deviation 61.3
|
77.5 cells/µL
Standard Deviation 201.6
|
-20.0 cells/µL
Standard Deviation 18.3
|
-125.0 cells/µL
Standard Deviation 205.1
|
-42.5 cells/µL
Standard Deviation 42.7
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h, FU (7 days post-dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group
Baseline (pre-dose Day 1)
|
209.5 cells 10^3/µL
Standard Deviation 45.9
|
204.0 cells 10^3/µL
Standard Deviation 15.7
|
193.0 cells 10^3/µL
Standard Deviation 31.9
|
223.0 cells 10^3/µL
Standard Deviation 21.6
|
215.8 cells 10^3/µL
Standard Deviation 64.0
|
203.8 cells 10^3/µL
Standard Deviation 7.0
|
202.3 cells 10^3/µL
Standard Deviation 54.5
|
160.1 cells 10^3/µL
Standard Deviation 100.8
|
204.5 cells 10^3/µL
Standard Deviation 67.2
|
215.8 cells 10^3/µL
Standard Deviation 55.6
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group
Change from BL at 24h
|
0.0 cells 10^3/µL
Standard Deviation 9.7
|
4.8 cells 10^3/µL
Standard Deviation 6.1
|
8.5 cells 10^3/µL
Standard Deviation 12.4
|
2.3 cells 10^3/µL
Standard Deviation 12.8
|
3.8 cells 10^3/µL
Standard Deviation 20.3
|
-14.5 cells 10^3/µL
Standard Deviation 29.7
|
22.3 cells 10^3/µL
Standard Deviation 13.5
|
23.0 cells 10^3/µL
Standard Deviation 22.8
|
4.0 cells 10^3/µL
Standard Deviation 7.1
|
0.3 cells 10^3/µL
Standard Deviation 9.0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group
Change from BL at FU
|
11.8 cells 10^3/µL
Standard Deviation 14.0
|
22.5 cells 10^3/µL
Standard Deviation 15.7
|
23.8 cells 10^3/µL
Standard Deviation 7.4
|
8.5 cells 10^3/µL
Standard Deviation 24.3
|
16.3 cells 10^3/µL
Standard Deviation 14.5
|
7.3 cells 10^3/µL
Standard Deviation 7.9
|
15.8 cells 10^3/µL
Standard Deviation 14.3
|
21.5 cells 10^3/µL
Standard Deviation 22.4
|
1.0 cells 10^3/µL
Standard Deviation 15.6
|
16.3 cells 10^3/µL
Standard Deviation 12.5
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group
Baseline (pre-dose Day 1)
|
23.3 cells/µL
Standard Deviation 5.2
|
25.0 cells/µL
Standard Deviation 10.5
|
15.0 cells/µL
Standard Deviation 5.8
|
30.0 cells/µL
Standard Deviation 18.3
|
15.0 cells/µL
Standard Deviation 10.0
|
32.5 cells/µL
Standard Deviation 15.0
|
20.0 cells/µL
Standard Deviation 11.5
|
22.5 cells/µL
Standard Deviation 5.0
|
65.0 cells/µL
Standard Deviation 63.6
|
25.0 cells/µL
Standard Deviation 17.3
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group
Change from BL at 24h
|
-5.0 cells/µL
Standard Deviation 8.4
|
0.0 cells/µL
Standard Deviation 8.9
|
2.5 cells/µL
Standard Deviation 5.0
|
-7.5 cells/µL
Standard Deviation 9.6
|
0.0 cells/µL
Standard Deviation 0.0
|
-5.0 cells/µL
Standard Deviation 10.0
|
2.5 cells/µL
Standard Deviation 5.0
|
5.0 cells/µL
Standard Deviation 5.8
|
-20.0 cells/µL
Standard Deviation 14.1
|
-2.5 cells/µL
Standard Deviation 9.6
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group
Change from BL at FU
|
0.0 cells/µL
Standard Deviation 12.6
|
-1.7 cells/µL
Standard Deviation 7.5
|
5.0 cells/µL
Standard Deviation 5.8
|
-5.0 cells/µL
Standard Deviation 10.0
|
7.5 cells/µL
Standard Deviation 9.6
|
-5.0 cells/µL
Standard Deviation 12.9
|
20.0 cells/µL
Standard Deviation 21.6
|
0.0 cells/µL
Standard Deviation 8.2
|
-15.0 cells/µL
Standard Deviation 21.2
|
-2.5 cells/µL
Standard Deviation 5.0
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group
Baseline (pre-dose Day 1)
|
445.0 cells/µL
Standard Deviation 78.2
|
496.7 cells/µL
Standard Deviation 71.7
|
407.5 cells/µL
Standard Deviation 79.3
|
455.0 cells/µL
Standard Deviation 81.9
|
397.5 cells/µL
Standard Deviation 133.0
|
467.5 cells/µL
Standard Deviation 98.8
|
462.5 cells/µL
Standard Deviation 147.1
|
470.0 cells/µL
Standard Deviation 87.6
|
550.0 cells/µL
Standard Deviation 70.7
|
512.5 cells/µL
Standard Deviation 133.5
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group
Change from BL at 24h
|
1.7 cells/µL
Standard Deviation 46.7
|
-81.7 cells/µL
Standard Deviation 54.9
|
20.0 cells/µL
Standard Deviation 78.3
|
-45.0 cells/µL
Standard Deviation 19.3
|
20.0 cells/µL
Standard Deviation 122.7
|
-62.5 cells/µL
Standard Deviation 185.5
|
-25.0 cells/µL
Standard Deviation 112.4
|
2.5 cells/µL
Standard Deviation 56.8
|
-45.0 cells/µL
Standard Deviation 21.2
|
-55.0 cells/µL
Standard Deviation 70.5
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group
Change from BL at FU
|
-21.7 cells/µL
Standard Deviation 91.5
|
-78.3 cells/µL
Standard Deviation 74.9
|
30.0 cells/µL
Standard Deviation 136.4
|
-70.0 cells/µL
Standard Deviation 94.9
|
5.0 cells/µL
Standard Deviation 128.2
|
-42.5 cells/µL
Standard Deviation 86.6
|
0.0 cells/µL
Standard Deviation 94.9
|
-47.5 cells/µL
Standard Deviation 63.4
|
-20.0 cells/µL
Standard Deviation 127.3
|
-110.0 cells/µL
Standard Deviation 128.3
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group
Baseline (pre-dose Day 1)
|
87.00 fL
Standard Deviation 0.62
|
89.32 fL
Standard Deviation 2.73
|
86.43 fL
Standard Deviation 1.29
|
89.02 fL
Standard Deviation 2.93
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group
Change from BL at Day 3
|
-0.05 fL
Standard Deviation 0.40
|
0.52 fL
Standard Deviation 1.15
|
0.55 fL
Standard Deviation 0.71
|
0.40 fL
Standard Deviation 1.08
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group
Change from BL at Day 8
|
-0.10 fL
Standard Deviation 1.30
|
-0.43 fL
Standard Deviation 0.28
|
0.32 fL
Standard Deviation 0.90
|
0.28 fL
Standard Deviation 0.95
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group
Change from BL at FU
|
0.60 fL
Standard Deviation 0.74
|
-0.55 fL
Standard Deviation 0.73
|
1.22 fL
Standard Deviation 1.31
|
0.65 fL
Standard Deviation 0.77
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group
Baseline (pre-dose Day 1)
|
13.68 g/dL
Standard Deviation 0.59
|
15.23 g/dL
Standard Deviation 1.38
|
15.68 g/dL
Standard Deviation 0.64
|
14.82 g/dL
Standard Deviation 0.67
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group
Change from BL at Day 3
|
1.05 g/dL
Standard Deviation 0.66
|
0.42 g/dL
Standard Deviation 0.74
|
0.17 g/dL
Standard Deviation 0.22
|
0.62 g/dL
Standard Deviation 0.50
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group
Change from BL at Day 8
|
1.35 g/dL
Standard Deviation 0.37
|
0.55 g/dL
Standard Deviation 1.22
|
0.27 g/dL
Standard Deviation 0.60
|
0.75 g/dL
Standard Deviation 0.83
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group
Change from BL at FU
|
0.30 g/dL
Standard Deviation 0.49
|
-0.05 g/dL
Standard Deviation 1.11
|
-0.38 g/dL
Standard Deviation 0.47
|
-0.35 g/dL
Standard Deviation 0.63
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD
Change from BL at Day 3
|
-0.435 cells 10^3/µL
Standard Deviation 0.631
|
0.480 cells 10^3/µL
Standard Deviation 0.787
|
0.895 cells 10^3/µL
Standard Deviation 0.940
|
0.277 cells 10^3/µL
Standard Deviation 0.932
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD
Change from BL at Day 8
|
0.223 cells 10^3/µL
Standard Deviation 2.237
|
0.480 cells 10^3/µL
Standard Deviation 0.252
|
0.795 cells 10^3/µL
Standard Deviation 0.178
|
0.563 cells 10^3/µL
Standard Deviation 0.983
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD
Baseline (pre-dose Day 1)
|
5.463 cells 10^3/µL
Standard Deviation 0.579
|
4.753 cells 10^3/µL
Standard Deviation 0.410
|
5.378 cells 10^3/µL
Standard Deviation 1.221
|
4.583 cells 10^3/µL
Standard Deviation 0.487
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD
Change from BL at FU
|
0.060 cells 10^3/µL
Standard Deviation 2.519
|
0.230 cells 10^3/µL
Standard Deviation 0.870
|
1.340 cells 10^3/µL
Standard Deviation 0.546
|
-0.140 cells 10^3/µL
Standard Deviation 0.930
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group
Baseline (pre-dose Day 1)
|
3077.5 cells/µL
Standard Deviation 569.5
|
2602.5 cells/µL
Standard Deviation 582.4
|
2935.0 cells/µL
Standard Deviation 966.6
|
2483.3 cells/µL
Standard Deviation 583.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group
Change from BL at Day 3
|
-567.5 cells/µL
Standard Deviation 667.9
|
350.0 cells/µL
Standard Deviation 602.4
|
437.5 cells/µL
Standard Deviation 505.3
|
81.7 cells/µL
Standard Deviation 540.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group
Change from BL at Day 8
|
105.0 cells/µL
Standard Deviation 2079.7
|
312.5 cells/µL
Standard Deviation 355.1
|
537.5 cells/µL
Standard Deviation 174.6
|
261.0 cells/µL
Standard Deviation 634.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group
Change from BL at FU
|
185.0 cells/µL
Standard Deviation 2317.4
|
177.5 cells/µL
Standard Deviation 827.7
|
1010.0 cells/µL
Standard Deviation 622.7
|
-75.0 cells/µL
Standard Deviation 532.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group
Baseline (pre-dose Day 1)
|
34.28 g/dL RBC
Standard Deviation 1.08
|
35.05 g/dL RBC
Standard Deviation 0.37
|
34.75 g/dL RBC
Standard Deviation 0.62
|
34.23 g/dL RBC
Standard Deviation 0.37
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group
Change from BL at Day 3
|
0.30 g/dL RBC
Standard Deviation 0.22
|
0.05 g/dL RBC
Standard Deviation 0.62
|
0.30 g/dL RBC
Standard Deviation 0.39
|
0.08 g/dL RBC
Standard Deviation 0.48
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group
Change from BL at Day 8
|
0.47 g/dL RBC
Standard Deviation 0.43
|
0.25 g/dL RBC
Standard Deviation 0.26
|
0.50 g/dL RBC
Standard Deviation 0.44
|
0.17 g/dL RBC
Standard Deviation 0.38
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group
Change from BL at FU
|
-0.08 g/dL RBC
Standard Deviation 0.33
|
0.00 g/dL RBC
Standard Deviation 0.27
|
0.00 g/dL RBC
Standard Deviation 0.65
|
-0.22 g/dL RBC
Standard Deviation 0.44
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group
Change from BL at Day 8
|
12.5 cells/µL
Standard Deviation 378.5
|
124.0 cells/µL
Standard Deviation 148.8
|
237.5 cells/µL
Standard Deviation 208.1
|
283.3 cells/µL
Standard Deviation 402.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group
Change from BL at FU
|
-55.0 cells/µL
Standard Deviation 257.5
|
39.0 cells/µL
Standard Deviation 382.3
|
262.5 cells/µL
Standard Deviation 220.2
|
5.0 cells/µL
Standard Deviation 465.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group
Baseline (pre-dose Day 1)
|
1627.5 cells/µL
Standard Deviation 656.0
|
1498.5 cells/µL
Standard Deviation 125.1
|
1750.0 cells/µL
Standard Deviation 187.4
|
1508.3 cells/µL
Standard Deviation 317.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group
Change from BL at Day 3
|
87.5 cells/µL
Standard Deviation 177.8
|
159.0 cells/µL
Standard Deviation 188.6
|
390.0 cells/µL
Standard Deviation 297.4
|
215.0 cells/µL
Standard Deviation 372.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group
Change from BL at Day 3
|
0.25 pg/cell
Standard Deviation 0.13
|
0.23 pg/cell
Standard Deviation 0.39
|
0.45 pg/cell
Standard Deviation 0.26
|
0.20 pg/cell
Standard Deviation 0.25
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group
Baseline (pre-dose Day 1)
|
29.80 pg/cell
Standard Deviation 0.91
|
31.33 pg/cell
Standard Deviation 1.24
|
30.03 pg/cell
Standard Deviation 0.49
|
30.47 pg/cell
Standard Deviation 0.97
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group
Change from BL at Day 8
|
0.40 pg/cell
Standard Deviation 0.40
|
0.12 pg/cell
Standard Deviation 0.22
|
0.57 pg/cell
Standard Deviation 0.62
|
0.25 pg/cell
Standard Deviation 0.33
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group
Change from BL at FU
|
0.15 pg/cell
Standard Deviation 0.47
|
-0.20 pg/cell
Standard Deviation 0.08
|
0.40 pg/cell
Standard Deviation 0.41
|
0.02 pg/cell
Standard Deviation 0.25
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group
Baseline (pre-dose Day 1)
|
4.588 cells 10^6/µL
Standard Deviation 0.108
|
4.858 cells 10^6/µL
Standard Deviation 0.380
|
5.217 cells 10^6/µL
Standard Deviation 0.138
|
4.873 cells 10^6/µL
Standard Deviation 0.360
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group
Change from BL at Day 3
|
0.313 cells 10^6/µL
Standard Deviation 0.234
|
0.100 cells 10^6/µL
Standard Deviation 0.193
|
-0.017 cells 10^6/µL
Standard Deviation 0.060
|
0.167 cells 10^6/µL
Standard Deviation 0.196
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group
Change from BL at Day 8
|
0.385 cells 10^6/µL
Standard Deviation 0.139
|
0.160 cells 10^6/µL
Standard Deviation 0.362
|
-0.007 cells 10^6/µL
Standard Deviation 0.144
|
0.198 cells 10^6/µL
Standard Deviation 0.249
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group
Change from BL at FU
|
0.075 cells 10^6/µL
Standard Deviation 0.099
|
0.020 cells 10^6/µL
Standard Deviation 0.350
|
-0.192 cells 10^6/µL
Standard Deviation 0.145
|
-0.120 cells 10^6/µL
Standard Deviation 0.237
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group
Baseline (pre-dose Day 1)
|
212.5 cells/µL
Standard Deviation 79.3
|
183.5 cells/µL
Standard Deviation 84.6
|
127.5 cells/µL
Standard Deviation 45.7
|
141.7 cells/µL
Standard Deviation 96.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group
Change from BL at Day 3
|
-40.0 cells/µL
Standard Deviation 52.3
|
-31.0 cells/µL
Standard Deviation 53.2
|
7.5 cells/µL
Standard Deviation 20.6
|
-28.3 cells/µL
Standard Deviation 43.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group
Change from BL at Day 8
|
-47.5 cells/µL
Standard Deviation 87.3
|
-28.5 cells/µL
Standard Deviation 66.0
|
-10.0 cells/µL
Standard Deviation 27.1
|
-22.7 cells/µL
Standard Deviation 56.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group
Change from BL at FU
|
-27.5 cells/µL
Standard Deviation 131.8
|
31.5 cells/µL
Standard Deviation 26.5
|
-17.5 cells/µL
Standard Deviation 27.5
|
-45.0 cells/µL
Standard Deviation 76.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group
Change from BL at FU
|
-52.5 cells/µL
Standard Deviation 176.7
|
-21.5 cells/µL
Standard Deviation 140.5
|
82.5 cells/µL
Standard Deviation 76.8
|
-43.3 cells/µL
Standard Deviation 85.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group
Baseline (pre-dose Day 1)
|
505.0 cells/µL
Standard Deviation 44.3
|
424.0 cells/µL
Standard Deviation 140.9
|
530.0 cells/µL
Standard Deviation 134.9
|
418.3 cells/µL
Standard Deviation 61.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group
Change from BL at Day 3
|
75.0 cells/µL
Standard Deviation 151.5
|
-11.5 cells/µL
Standard Deviation 142.6
|
57.5 cells/µL
Standard Deviation 115.0
|
1.7 cells/µL
Standard Deviation 64.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group
Change from BL at Day 8
|
137.5 cells/µL
Standard Deviation 374.6
|
76.0 cells/µL
Standard Deviation 95.3
|
27.5 cells/µL
Standard Deviation 42.7
|
24.3 cells/µL
Standard Deviation 53.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group
Change from BL at Day 3
|
15.5 cells 10^3/µL
Standard Deviation 14.5
|
17.5 cells 10^3/µL
Standard Deviation 9.5
|
27.5 cells 10^3/µL
Standard Deviation 8.4
|
17.3 cells 10^3/µL
Standard Deviation 15.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group
Change from BL at Day 8
|
44.8 cells 10^3/µL
Standard Deviation 37.6
|
4.8 cells 10^3/µL
Standard Deviation 22.3
|
31.3 cells 10^3/µL
Standard Deviation 13.9
|
29.5 cells 10^3/µL
Standard Deviation 12.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group
Baseline (pre-dose Day 1)
|
207.3 cells 10^3/µL
Standard Deviation 24.6
|
211.5 cells 10^3/µL
Standard Deviation 41.2
|
199.8 cells 10^3/µL
Standard Deviation 25.6
|
206.7 cells 10^3/µL
Standard Deviation 48.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group
Change from BL at FU
|
63.8 cells 10^3/µL
Standard Deviation 41.3
|
5.5 cells 10^3/µL
Standard Deviation 21.9
|
33.8 cells 10^3/µL
Standard Deviation 20.0
|
21.7 cells 10^3/µL
Standard Deviation 10.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group
Baseline (pre-dose Day 1)
|
30.0 cells/µL
Standard Deviation 8.2
|
34.0 cells/µL
Standard Deviation 10.8
|
20.0 cells/µL
Standard Deviation 11.5
|
23.3 cells/µL
Standard Deviation 10.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group
Change from BL at Day 3
|
7.5 cells/µL
Standard Deviation 17.1
|
8.5 cells/µL
Standard Deviation 17.4
|
2.5 cells/µL
Standard Deviation 5.0
|
3.3 cells/µL
Standard Deviation 8.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group
Change from BL at Day 8
|
12.5 cells/µL
Standard Deviation 20.6
|
-6.5 cells/µL
Standard Deviation 17.0
|
5.0 cells/µL
Standard Deviation 12.9
|
4.0 cells/µL
Standard Deviation 14.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group
Change from BL at FU
|
7.5 cells/µL
Standard Deviation 15.0
|
1.0 cells/µL
Standard Deviation 6.6
|
2.5 cells/µL
Standard Deviation 12.6
|
5.0 cells/µL
Standard Deviation 18.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group
Change from BL at FU
|
0.3 U/L
Standard Deviation 1.0
|
3.3 U/L
Standard Deviation 5.8
|
2.8 U/L
Standard Deviation 6.2
|
4.8 U/L
Standard Deviation 7.6
|
0.3 U/L
Standard Deviation 4.9
|
0.5 U/L
Standard Deviation 7.6
|
1.3 U/L
Standard Deviation 3.6
|
1.0 U/L
Standard Deviation 3.7
|
3.5 U/L
Standard Deviation 6.4
|
0.0 U/L
Standard Deviation 1.4
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group
Baseline (pre-dose Day 1)
|
20.5 U/L
Standard Deviation 5.9
|
16.8 U/L
Standard Deviation 2.7
|
19.3 U/L
Standard Deviation 4.3
|
17.5 U/L
Standard Deviation 3.8
|
18.3 U/L
Standard Deviation 9.2
|
20.8 U/L
Standard Deviation 4.4
|
18.8 U/L
Standard Deviation 6.1
|
17.0 U/L
Standard Deviation 2.9
|
19.5 U/L
Standard Deviation 2.1
|
18.5 U/L
Standard Deviation 4.8
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group
Change from BL at 24h
|
-2.7 U/L
Standard Deviation 1.2
|
0.3 U/L
Standard Deviation 2.1
|
-0.5 U/L
Standard Deviation 1.3
|
1.8 U/L
Standard Deviation 3.0
|
-2.5 U/L
Standard Deviation 4.7
|
-0.3 U/L
Standard Deviation 1.0
|
-1.0 U/L
Standard Deviation 3.3
|
0.5 U/L
Standard Deviation 2.5
|
-1.0 U/L
Standard Deviation 2.8
|
-1.0 U/L
Standard Deviation 2.2
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group
Baseline (pre-dose Day 1)
|
67.5 g/L
Standard Deviation 4.9
|
65.5 g/L
Standard Deviation 5.2
|
67.0 g/L
Standard Deviation 4.1
|
67.3 g/L
Standard Deviation 2.2
|
65.3 g/L
Standard Deviation 5.0
|
66.0 g/L
Standard Deviation 1.8
|
66.3 g/L
Standard Deviation 3.5
|
66.0 g/L
Standard Deviation 1.4
|
66.5 g/L
Standard Deviation 2.1
|
66.3 g/L
Standard Deviation 5.4
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group
Change from BL at 24h
|
1.3 g/L
Standard Deviation 2.7
|
3.7 g/L
Standard Deviation 3.6
|
1.5 g/L
Standard Deviation 1.0
|
3.0 g/L
Standard Deviation 2.4
|
2.8 g/L
Standard Deviation 4.0
|
6.0 g/L
Standard Deviation 1.6
|
3.0 g/L
Standard Deviation 5.0
|
9.3 g/L
Standard Deviation 4.8
|
2.5 g/L
Standard Deviation 4.9
|
2.3 g/L
Standard Deviation 4.6
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group
Change from BL at FU
|
1.5 g/L
Standard Deviation 2.9
|
3.3 g/L
Standard Deviation 3.1
|
4.0 g/L
Standard Deviation 2.2
|
1.8 g/L
Standard Deviation 3.9
|
3.3 g/L
Standard Deviation 1.7
|
0.8 g/L
Standard Deviation 1.7
|
0.0 g/L
Standard Deviation 2.2
|
4.8 g/L
Standard Deviation 3.3
|
1.0 g/L
Standard Deviation 1.4
|
2.3 g/L
Standard Deviation 3.2
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group
Baseline (pre-dose Day 1)
|
23.5 U/L
Standard Deviation 26.7
|
19.0 U/L
Standard Deviation 14.1
|
24.0 U/L
Standard Deviation 20.0
|
23.0 U/L
Standard Deviation 16.2
|
12.0 U/L
Standard Deviation 6.8
|
17.3 U/L
Standard Deviation 12.1
|
30.0 U/L
Standard Deviation 30.8
|
21.3 U/L
Standard Deviation 17.2
|
29.0 U/L
Standard Deviation 14.1
|
13.5 U/L
Standard Deviation 5.1
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group
Change from BL at 24h
|
-0.8 U/L
Standard Deviation 1.7
|
1.2 U/L
Standard Deviation 2.1
|
0.0 U/L
Standard Deviation 0.8
|
0.8 U/L
Standard Deviation 1.7
|
0.3 U/L
Standard Deviation 1.3
|
1.3 U/L
Standard Deviation 0.5
|
-0.5 U/L
Standard Deviation 4.4
|
3.8 U/L
Standard Deviation 3.1
|
0.0 U/L
Standard Deviation 2.8
|
0.8 U/L
Standard Deviation 1.0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group
Change from BL at FU
|
-4.0 U/L
Standard Deviation 13.8
|
10.0 U/L
Standard Deviation 16.1
|
-1.3 U/L
Standard Deviation 4.5
|
13.8 U/L
Standard Deviation 18.4
|
2.5 U/L
Standard Deviation 2.4
|
11.3 U/L
Standard Deviation 20.5
|
-7.3 U/L
Standard Deviation 15.6
|
1.8 U/L
Standard Deviation 2.5
|
3.5 U/L
Standard Deviation 3.5
|
1.0 U/L
Standard Deviation 0.8
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group
Baseline (pre-dose Day 1)
|
62.0 U/L
Standard Deviation 18.6
|
64.0 U/L
Standard Deviation 19.8
|
66.0 U/L
Standard Deviation 18.5
|
75.0 U/L
Standard Deviation 32.2
|
66.0 U/L
Standard Deviation 25.0
|
68.3 U/L
Standard Deviation 28.0
|
53.3 U/L
Standard Deviation 10.2
|
49.0 U/L
Standard Deviation 8.9
|
54.5 U/L
Standard Deviation 2.1
|
62.3 U/L
Standard Deviation 21.7
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group
Change from BL at 24h
|
-0.2 U/L
Standard Deviation 3.0
|
1.7 U/L
Standard Deviation 3.5
|
1.0 U/L
Standard Deviation 2.8
|
-1.8 U/L
Standard Deviation 8.1
|
1.0 U/L
Standard Deviation 4.7
|
3.8 U/L
Standard Deviation 4.6
|
1.3 U/L
Standard Deviation 3.6
|
6.8 U/L
Standard Deviation 3.5
|
2.0 U/L
Standard Deviation 2.8
|
0.8 U/L
Standard Deviation 3.6
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group
Change from BL at FU
|
-1.5 U/L
Standard Deviation 9.0
|
1.7 U/L
Standard Deviation 6.3
|
1.8 U/L
Standard Deviation 3.5
|
-3.8 U/L
Standard Deviation 18.2
|
1.5 U/L
Standard Deviation 3.4
|
-1.5 U/L
Standard Deviation 11.3
|
-2.0 U/L
Standard Deviation 5.4
|
4.3 U/L
Standard Deviation 1.5
|
2.0 U/L
Standard Deviation 2.8
|
-0.8 U/L
Standard Deviation 4.9
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group
Baseline (pre-dose Day 1)
|
0.927 mg/dL
Standard Deviation 0.058
|
0.768 mg/dL
Standard Deviation 0.108
|
0.903 mg/dL
Standard Deviation 0.028
|
0.810 mg/dL
Standard Deviation 0.091
|
0.838 mg/dL
Standard Deviation 0.035
|
0.735 mg/dL
Standard Deviation 0.108
|
0.918 mg/dL
Standard Deviation 0.043
|
0.838 mg/dL
Standard Deviation 0.213
|
0.935 mg/dL
Standard Deviation 0.078
|
0.863 mg/dL
Standard Deviation 0.024
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group
Change from BL at 24h
|
0.023 mg/dL
Standard Deviation 0.050
|
0.067 mg/dL
Standard Deviation 0.033
|
0.080 mg/dL
Standard Deviation 0.054
|
0.053 mg/dL
Standard Deviation 0.076
|
0.040 mg/dL
Standard Deviation 0.041
|
0.115 mg/dL
Standard Deviation 0.025
|
0.090 mg/dL
Standard Deviation 0.043
|
0.075 mg/dL
Standard Deviation 0.112
|
0.015 mg/dL
Standard Deviation 0.106
|
0.038 mg/dL
Standard Deviation 0.071
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group
Change from BL at FU
|
-0.003 mg/dL
Standard Deviation 0.048
|
0.065 mg/dL
Standard Deviation 0.048
|
0.012 mg/dL
Standard Deviation 0.039
|
0.073 mg/dL
Standard Deviation 0.056
|
0.088 mg/dL
Standard Deviation 0.068
|
0.063 mg/dL
Standard Deviation 0.028
|
-0.020 mg/dL
Standard Deviation 0.096
|
-0.017 mg/dL
Standard Deviation 0.085
|
-0.080 mg/dL
Standard Deviation 0.071
|
0.063 mg/dL
Standard Deviation 0.068
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group
Baseline (pre-dose Day 1)
|
102.7 mmol/L
Standard Deviation 2.7
|
104.0 mmol/L
Standard Deviation 1.7
|
103.8 mmol/L
Standard Deviation 1.7
|
104.0 mmol/L
Standard Deviation 0.8
|
102.3 mmol/L
Standard Deviation 2.4
|
103.0 mmol/L
Standard Deviation 1.4
|
103.3 mmol/L
Standard Deviation 1.5
|
103.8 mmol/L
Standard Deviation 1.7
|
100.5 mmol/L
Standard Deviation 2.1
|
101.5 mmol/L
Standard Deviation 2.1
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group
Change from BL at 24h
|
-0.5 mmol/L
Standard Deviation 1.4
|
-2.5 mmol/L
Standard Deviation 1.4
|
-1.5 mmol/L
Standard Deviation 2.5
|
-3.5 mmol/L
Standard Deviation 0.6
|
0.0 mmol/L
Standard Deviation 1.8
|
-2.8 mmol/L
Standard Deviation 1.0
|
-1.3 mmol/L
Standard Deviation 1.0
|
-3.5 mmol/L
Standard Deviation 1.7
|
2.0 mmol/L
Standard Deviation 0.0
|
-0.5 mmol/L
Standard Deviation 1.3
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group
Change from BL at FU
|
-1.5 mmol/L
Standard Deviation 3.5
|
-3.2 mmol/L
Standard Deviation 2.2
|
-2.5 mmol/L
Standard Deviation 2.1
|
-3.5 mmol/L
Standard Deviation 1.3
|
-0.8 mmol/L
Standard Deviation 2.2
|
-2.3 mmol/L
Standard Deviation 2.2
|
-0.8 mmol/L
Standard Deviation 3.5
|
-3.0 mmol/L
Standard Deviation 0.0
|
3.5 mmol/L
Standard Deviation 3.5
|
0.0 mmol/L
Standard Deviation 2.7
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group
Change from BL at 24h
|
0.30 mg/dL
Standard Deviation 0.26
|
0.12 mg/dL
Standard Deviation 0.08
|
0.40 mg/dL
Standard Deviation 0.08
|
0.38 mg/dL
Standard Deviation 0.13
|
-0.00 mg/dL
Standard Deviation 0.18
|
0.28 mg/dL
Standard Deviation 0.10
|
-0.03 mg/dL
Standard Deviation 0.15
|
0.31 mg/dL
Standard Deviation 0.09
|
0.15 mg/dL
Standard Deviation 0.07
|
0.27 mg/dL
Standard Deviation 0.17
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group
Change from BL at FU
|
0.13 mg/dL
Standard Deviation 0.42
|
-0.02 mg/dL
Standard Deviation 0.40
|
0.05 mg/dL
Standard Deviation 0.13
|
0.13 mg/dL
Standard Deviation 0.13
|
-0.18 mg/dL
Standard Deviation 0.33
|
0.20 mg/dL
Standard Deviation 0.18
|
0.00 mg/dL
Standard Deviation 0.29
|
0.21 mg/dL
Standard Deviation 0.10
|
0.10 mg/dL
Standard Deviation 0.14
|
-0.10 mg/dL
Standard Deviation 0.56
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group
Baseline (pre-dose Day 1)
|
0.82 mg/dL
Standard Deviation 0.32
|
0.75 mg/dL
Standard Deviation 0.60
|
1.03 mg/dL
Standard Deviation 0.83
|
0.68 mg/dL
Standard Deviation 0.33
|
1.18 mg/dL
Standard Deviation 1.03
|
0.53 mg/dL
Standard Deviation 0.13
|
0.63 mg/dL
Standard Deviation 0.22
|
0.31 mg/dL
Standard Deviation 0.19
|
0.45 mg/dL
Standard Deviation 0.21
|
1.10 mg/dL
Standard Deviation 1.33
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group
Change from BL at 24h
|
-1.2 U/L
Standard Deviation 2.2
|
-0.3 U/L
Standard Deviation 3.2
|
0.8 U/L
Standard Deviation 2.9
|
-1.3 U/L
Standard Deviation 3.5
|
1.3 U/L
Standard Deviation 1.3
|
-0.3 U/L
Standard Deviation 2.8
|
-2.0 U/L
Standard Deviation 3.6
|
0.3 U/L
Standard Deviation 3.9
|
1.5 U/L
Standard Deviation 2.1
|
1.5 U/L
Standard Deviation 1.0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group
Baseline (pre-dose Day 1)
|
20.2 U/L
Standard Deviation 11.3
|
17.2 U/L
Standard Deviation 6.9
|
19.3 U/L
Standard Deviation 3.2
|
20.0 U/L
Standard Deviation 10.1
|
15.0 U/L
Standard Deviation 6.9
|
19.3 U/L
Standard Deviation 6.6
|
22.8 U/L
Standard Deviation 12.8
|
17.8 U/L
Standard Deviation 6.8
|
19.0 U/L
Standard Deviation 1.4
|
15.0 U/L
Standard Deviation 5.7
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group
Change from BL at FU
|
-1.0 U/L
Standard Deviation 4.5
|
5.7 U/L
Standard Deviation 17.7
|
2.3 U/L
Standard Deviation 7.8
|
8.3 U/L
Standard Deviation 18.0
|
1.8 U/L
Standard Deviation 2.6
|
6.0 U/L
Standard Deviation 21.5
|
-2.3 U/L
Standard Deviation 5.7
|
-1.0 U/L
Standard Deviation 2.9
|
7.5 U/L
Standard Deviation 9.2
|
1.8 U/L
Standard Deviation 2.1
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group
Baseline (pre-dose Day 1)
|
118.2 U/L
Standard Deviation 39.3
|
78.7 U/L
Standard Deviation 5.9
|
181.8 U/L
Standard Deviation 59.3
|
78.8 U/L
Standard Deviation 13.4
|
209.3 U/L
Standard Deviation 223.6
|
82.3 U/L
Standard Deviation 28.0
|
68.5 U/L
Standard Deviation 49.5
|
89.5 U/L
Standard Deviation 45.4
|
82.5 U/L
Standard Deviation 89.8
|
81.3 U/L
Standard Deviation 29.4
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group
Change from BL at 24h
|
-34.3 U/L
Standard Deviation 23.1
|
-14.0 U/L
Standard Deviation 3.3
|
-51.0 U/L
Standard Deviation 34.6
|
-12.8 U/L
Standard Deviation 1.9
|
-97.8 U/L
Standard Deviation 137.1
|
-15.5 U/L
Standard Deviation 14.1
|
-14.0 U/L
Standard Deviation 23.6
|
-14.8 U/L
Standard Deviation 26.9
|
-31.5 U/L
Standard Deviation 43.1
|
-14.8 U/L
Standard Deviation 8.3
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group
Change from BL at FU
|
13.0 U/L
Standard Deviation 43.7
|
16.7 U/L
Standard Deviation 35.7
|
-17.3 U/L
Standard Deviation 88.6
|
24.5 U/L
Standard Deviation 39.4
|
-110.0 U/L
Standard Deviation 173.1
|
6.0 U/L
Standard Deviation 7.5
|
15.8 U/L
Standard Deviation 16.9
|
7.0 U/L
Standard Deviation 61.9
|
21.5 U/L
Standard Deviation 17.7
|
18.0 U/L
Standard Deviation 31.2
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group
Baseline (pre-dose Day 1)
|
27.5 mg/dL
Standard Deviation 9.3
|
24.7 mg/dL
Standard Deviation 4.5
|
30.0 mg/dL
Standard Deviation 8.4
|
26.0 mg/dL
Standard Deviation 7.3
|
24.0 mg/dL
Standard Deviation 2.4
|
25.3 mg/dL
Standard Deviation 4.1
|
29.3 mg/dL
Standard Deviation 10.6
|
34.8 mg/dL
Standard Deviation 7.7
|
38.5 mg/dL
Standard Deviation 6.4
|
25.8 mg/dL
Standard Deviation 5.7
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group
Change from BL at 24h
|
0.0 mg/dL
Standard Deviation 3.9
|
0.2 mg/dL
Standard Deviation 4.4
|
-2.5 mg/dL
Standard Deviation 5.0
|
-0.3 mg/dL
Standard Deviation 2.5
|
0.0 mg/dL
Standard Deviation 2.8
|
-0.5 mg/dL
Standard Deviation 5.2
|
-1.0 mg/dL
Standard Deviation 4.7
|
-4.0 mg/dL
Standard Deviation 8.6
|
-9.0 mg/dL
Standard Deviation 1.4
|
-0.5 mg/dL
Standard Deviation 3.3
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group
Change from BL at FU
|
1.2 mg/dL
Standard Deviation 7.1
|
0.5 mg/dL
Standard Deviation 7.7
|
-0.8 mg/dL
Standard Deviation 3.9
|
2.3 mg/dL
Standard Deviation 7.7
|
0.3 mg/dL
Standard Deviation 4.5
|
-2.3 mg/dL
Standard Deviation 7.3
|
-0.3 mg/dL
Standard Deviation 5.4
|
-6.8 mg/dL
Standard Deviation 11.8
|
-8.0 mg/dL
Standard Deviation 4.2
|
-1.5 mg/dL
Standard Deviation 4.7
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group
Baseline (pre-dose Day 1)
|
141.8 mmol/L
Standard Deviation 1.0
|
142.5 mmol/L
Standard Deviation 1.2
|
141.5 mmol/L
Standard Deviation 0.6
|
142.8 mmol/L
Standard Deviation 1.0
|
141.5 mmol/L
Standard Deviation 1.7
|
142.0 mmol/L
Standard Deviation 0.8
|
142.3 mmol/L
Standard Deviation 1.3
|
143.3 mmol/L
Standard Deviation 1.0
|
139.5 mmol/L
Standard Deviation 0.7
|
140.5 mmol/L
Standard Deviation 1.0
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group
Change from BL at 24h
|
-0.2 mmol/L
Standard Deviation 1.6
|
-0.7 mmol/L
Standard Deviation 0.8
|
-0.3 mmol/L
Standard Deviation 2.2
|
-2.0 mmol/L
Standard Deviation 1.4
|
-0.8 mmol/L
Standard Deviation 2.2
|
-1.0 mmol/L
Standard Deviation 0.8
|
0.5 mmol/L
Standard Deviation 0.6
|
-1.3 mmol/L
Standard Deviation 1.0
|
2.5 mmol/L
Standard Deviation 2.1
|
1.0 mmol/L
Standard Deviation 2.6
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group
Change from BL at FU
|
-0.3 mmol/L
Standard Deviation 2.4
|
-1.8 mmol/L
Standard Deviation 2.0
|
0.0 mmol/L
Standard Deviation 2.7
|
-2.3 mmol/L
Standard Deviation 2.2
|
0.8 mmol/L
Standard Deviation 1.3
|
-2.0 mmol/L
Standard Deviation 0.8
|
0.5 mmol/L
Standard Deviation 2.4
|
-2.8 mmol/L
Standard Deviation 1.3
|
4.5 mmol/L
Standard Deviation 0.7
|
1.8 mmol/L
Standard Deviation 0.5
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group
Baseline (pre-dose Day 1)
|
4.25 mmol/L
Standard Deviation 0.18
|
4.27 mmol/L
Standard Deviation 0.18
|
4.25 mmol/L
Standard Deviation 0.13
|
4.18 mmol/L
Standard Deviation 0.25
|
4.03 mmol/L
Standard Deviation 0.19
|
4.33 mmol/L
Standard Deviation 0.13
|
4.28 mmol/L
Standard Deviation 0.32
|
4.50 mmol/L
Standard Deviation 0.18
|
4.00 mmol/L
Standard Deviation 0.00
|
4.20 mmol/L
Standard Deviation 0.22
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group
Change from BL at 24h
|
0.17 mmol/L
Standard Deviation 0.18
|
0.17 mmol/L
Standard Deviation 0.21
|
0.07 mmol/L
Standard Deviation 0.31
|
0.23 mmol/L
Standard Deviation 0.33
|
0.30 mmol/L
Standard Deviation 0.22
|
-0.05 mmol/L
Standard Deviation 0.26
|
0.12 mmol/L
Standard Deviation 0.10
|
-0.10 mmol/L
Standard Deviation 0.16
|
0.25 mmol/L
Standard Deviation 0.07
|
0.15 mmol/L
Standard Deviation 0.34
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group
Change from BL at FU
|
0.25 mmol/L
Standard Deviation 0.10
|
0.10 mmol/L
Standard Deviation 0.26
|
0.30 mmol/L
Standard Deviation 0.22
|
0.20 mmol/L
Standard Deviation 0.29
|
0.50 mmol/L
Standard Deviation 0.22
|
0.10 mmol/L
Standard Deviation 0.27
|
0.08 mmol/L
Standard Deviation 0.36
|
-0.05 mmol/L
Standard Deviation 0.10
|
0.30 mmol/L
Standard Deviation 0.14
|
0.33 mmol/L
Standard Deviation 0.17
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group
Baseline (pre-dose Day 1)
|
1.042 mmol/L
Standard Deviation 0.066
|
0.998 mmol/L
Standard Deviation 0.122
|
1.120 mmol/L
Standard Deviation 0.117
|
1.085 mmol/L
Standard Deviation 0.133
|
1.023 mmol/L
Standard Deviation 0.081
|
0.983 mmol/L
Standard Deviation 0.165
|
1.088 mmol/L
Standard Deviation 0.142
|
1.128 mmol/L
Standard Deviation 0.193
|
1.410 mmol/L
Standard Deviation 0.552
|
1.105 mmol/L
Standard Deviation 0.154
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group
Change from BL at 24h
|
0.033 mmol/L
Standard Deviation 0.126
|
-0.045 mmol/L
Standard Deviation 0.094
|
-0.035 mmol/L
Standard Deviation 0.169
|
-0.133 mmol/L
Standard Deviation 0.105
|
0.045 mmol/L
Standard Deviation 0.172
|
-0.060 mmol/L
Standard Deviation 0.111
|
0.032 mmol/L
Standard Deviation 0.116
|
-0.090 mmol/L
Standard Deviation 0.164
|
-0.180 mmol/L
Standard Deviation 0.999
|
-0.015 mmol/L
Standard Deviation 0.079
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group
Change from BL at FU
|
-0.020 mmol/L
Standard Deviation 0.116
|
0.030 mmol/L
Standard Deviation 0.172
|
-0.077 mmol/L
Standard Deviation 0.126
|
-0.018 mmol/L
Standard Deviation 0.182
|
0.003 mmol/L
Standard Deviation 0.046
|
-0.070 mmol/L
Standard Deviation 0.153
|
-0.090 mmol/L
Standard Deviation 0.121
|
-0.105 mmol/L
Standard Deviation 0.135
|
-0.395 mmol/L
Standard Deviation 0.205
|
-0.080 mmol/L
Standard Deviation 0.097
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group
Baseline (pre-dose Day 1)
|
2.380 mmol/L
Standard Deviation 0.073
|
2.303 mmol/L
Standard Deviation 0.087
|
2.290 mmol/L
Standard Deviation 0.114
|
2.288 mmol/L
Standard Deviation 0.030
|
2.373 mmol/L
Standard Deviation 0.116
|
2.358 mmol/L
Standard Deviation 0.069
|
2.353 mmol/L
Standard Deviation 0.102
|
2.323 mmol/L
Standard Deviation 0.044
|
2.340 mmol/L
Standard Deviation 0.000
|
2.360 mmol/L
Standard Deviation 0.118
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group
Change from BL at 24h
|
0.033 mmol/L
Standard Deviation 0.045
|
0.095 mmol/L
Standard Deviation 0.066
|
0.098 mmol/L
Standard Deviation 0.050
|
0.093 mmol/L
Standard Deviation 0.028
|
0.058 mmol/L
Standard Deviation 0.105
|
0.085 mmol/L
Standard Deviation 0.059
|
0.078 mmol/L
Standard Deviation 0.075
|
0.148 mmol/L
Standard Deviation 0.055
|
-0.005 mmol/L
Standard Deviation 0.021
|
0.075 mmol/L
Standard Deviation 0.088
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group
Change from BL at FU
|
0.010 mmol/L
Standard Deviation 0.041
|
0.062 mmol/L
Standard Deviation 0.075
|
0.085 mmol/L
Standard Deviation 0.070
|
0.073 mmol/L
Standard Deviation 0.098
|
0.042 mmol/L
Standard Deviation 0.030
|
-0.032 mmol/L
Standard Deviation 0.006
|
-0.005 mmol/L
Standard Deviation 0.033
|
0.090 mmol/L
Standard Deviation 0.059
|
-0.065 mmol/L
Standard Deviation 0.049
|
0.055 mmol/L
Standard Deviation 0.039
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group
Baseline (pre-dose Day 1)
|
5.52 mg/dL
Standard Deviation 0.84
|
4.85 mg/dL
Standard Deviation 0.84
|
5.75 mg/dL
Standard Deviation 0.42
|
4.80 mg/dL
Standard Deviation 0.37
|
5.48 mg/dL
Standard Deviation 0.82
|
4.75 mg/dL
Standard Deviation 0.79
|
5.48 mg/dL
Standard Deviation 1.07
|
5.10 mg/dL
Standard Deviation 0.96
|
5.45 mg/dL
Standard Deviation 0.21
|
5.50 mg/dL
Standard Deviation 1.41
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group
Change from BL at 24h
|
-0.25 mg/dL
Standard Deviation 0.40
|
-0.13 mg/dL
Standard Deviation 0.23
|
-0.28 mg/dL
Standard Deviation 0.25
|
-0.20 mg/dL
Standard Deviation 0.24
|
-0.30 mg/dL
Standard Deviation 0.12
|
-0.25 mg/dL
Standard Deviation 0.24
|
-0.20 mg/dL
Standard Deviation 0.32
|
0.15 mg/dL
Standard Deviation 0.42
|
-0.60 mg/dL
Standard Deviation 0.28
|
-0.28 mg/dL
Standard Deviation 0.40
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group
Change from BL at FU
|
0.28 mg/dL
Standard Deviation 0.26
|
0.32 mg/dL
Standard Deviation 0.50
|
0.22 mg/dL
Standard Deviation 0.79
|
0.40 mg/dL
Standard Deviation 0.43
|
0.35 mg/dL
Standard Deviation 0.53
|
0.30 mg/dL
Standard Deviation 0.08
|
0.18 mg/dL
Standard Deviation 0.68
|
0.23 mg/dL
Standard Deviation 0.22
|
0.40 mg/dL
Standard Deviation 0.28
|
0.33 mg/dL
Standard Deviation 0.51
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group
Baseline (pre-dose Day 1)
|
3.65 pg/mL
Standard Deviation 0.35
|
3.23 pg/mL
Standard Deviation 0.12
|
3.73 pg/mL
Standard Deviation 0.21
|
3.40 pg/mL
Standard Deviation 0.22
|
3.48 pg/mL
Standard Deviation 0.30
|
3.18 pg/mL
Standard Deviation 0.17
|
3.18 pg/mL
Standard Deviation 0.17
|
3.33 pg/mL
Standard Deviation 0.19
|
3.60 pg/mL
Standard Deviation 0.14
|
3.63 pg/mL
Standard Deviation 0.41
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group
Change from BL at 24h
|
-0.35 pg/mL
Standard Deviation 0.28
|
-0.10 pg/mL
Standard Deviation 0.24
|
-0.22 pg/mL
Standard Deviation 0.17
|
0.05 pg/mL
Standard Deviation 0.31
|
-0.07 pg/mL
Standard Deviation 0.10
|
-0.23 pg/mL
Standard Deviation 0.10
|
-0.23 pg/mL
Standard Deviation 0.36
|
-0.13 pg/mL
Standard Deviation 0.15
|
-0.40 pg/mL
Standard Deviation 0.00
|
-0.25 pg/mL
Standard Deviation 0.17
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group
Change from BL at FU
|
-0.30 pg/mL
Standard Deviation 0.28
|
0.42 pg/mL
Standard Deviation 0.23
|
-0.23 pg/mL
Standard Deviation 0.13
|
0.30 pg/mL
Standard Deviation 0.23
|
-0.13 pg/mL
Standard Deviation 0.17
|
0.50 pg/mL
Standard Deviation 0.34
|
0.05 pg/mL
Standard Deviation 0.13
|
0.20 pg/mL
Standard Deviation 0.08
|
-0.30 pg/mL
Standard Deviation 0.14
|
-0.28 pg/mL
Standard Deviation 0.15
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group
Baseline (pre-dose Day 1)
|
31.0 U/L
Standard Deviation 8.2
|
34.8 U/L
Standard Deviation 16.2
|
39.0 U/L
Standard Deviation 9.8
|
29.3 U/L
Standard Deviation 12.7
|
27.3 U/L
Standard Deviation 7.5
|
33.0 U/L
Standard Deviation 9.2
|
30.0 U/L
Standard Deviation 8.0
|
25.5 U/L
Standard Deviation 6.2
|
42.0 U/L
Standard Deviation 14.1
|
31.1 U/L
Standard Deviation 11.8
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group
Change from BL at 24h
|
-1.5 U/L
Standard Deviation 3.1
|
-7.5 U/L
Standard Deviation 18.5
|
-6.3 U/L
Standard Deviation 6.8
|
-1.8 U/L
Standard Deviation 2.9
|
1.3 U/L
Standard Deviation 0.5
|
7.3 U/L
Standard Deviation 16.5
|
-1.3 U/L
Standard Deviation 3.4
|
-4.8 U/L
Standard Deviation 5.1
|
-0.5 U/L
Standard Deviation 2.1
|
-2.5 U/L
Standard Deviation 5.1
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group
Change from BL at FU
|
-1.0 U/L
Standard Deviation 2.3
|
-1.0 U/L
Standard Deviation 5.5
|
-4.5 U/L
Standard Deviation 12.4
|
8.0 U/L
Standard Deviation 27.2
|
1.5 U/L
Standard Deviation 3.0
|
-5.0 U/L
Standard Deviation 3.7
|
-2.0 U/L
Standard Deviation 6.5
|
9.3 U/L
Standard Deviation 19.8
|
-7.0 U/L
Standard Deviation 4.2
|
-2.5 U/L
Standard Deviation 3.0
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group
Baseline (pre-dose Day 1)
|
85.0 mg/dL
Standard Deviation 7.3
|
86.8 mg/dL
Standard Deviation 8.9
|
84.8 mg/dL
Standard Deviation 7.4
|
88.5 mg/dL
Standard Deviation 12.2
|
77.8 mg/dL
Standard Deviation 5.7
|
86.3 mg/dL
Standard Deviation 9.4
|
87.0 mg/dL
Standard Deviation 4.2
|
95.5 mg/dL
Standard Deviation 18.7
|
84.0 mg/dL
Standard Deviation 5.7
|
78.8 mg/dL
Standard Deviation 3.8
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group
Change from BL at 24h
|
-1.0 mg/dL
Standard Deviation 3.2
|
1.2 mg/dL
Standard Deviation 5.2
|
2.0 mg/dL
Standard Deviation 3.7
|
-2.0 mg/dL
Standard Deviation 3.2
|
7.0 mg/dL
Standard Deviation 4.5
|
-1.0 mg/dL
Standard Deviation 1.4
|
0.5 mg/dL
Standard Deviation 3.1
|
-2.3 mg/dL
Standard Deviation 1.0
|
4.0 mg/dL
Standard Deviation 1.4
|
3.3 mg/dL
Standard Deviation 1.9
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group
Change from BL at FU
|
-0.2 mg/dL
Standard Deviation 7.0
|
5.5 mg/dL
Standard Deviation 6.9
|
-0.3 mg/dL
Standard Deviation 7.7
|
6.3 mg/dL
Standard Deviation 6.7
|
7.3 mg/dL
Standard Deviation 6.2
|
0.5 mg/dL
Standard Deviation 5.9
|
-1.3 mg/dL
Standard Deviation 5.4
|
-1.5 mg/dL
Standard Deviation 1.7
|
2.0 mg/dL
Standard Deviation 8.5
|
6.3 mg/dL
Standard Deviation 3.8
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group
Change from BL at FU
|
0.2 g/L
Standard Deviation 1.8
|
2.0 g/L
Standard Deviation 1.4
|
2.3 g/L
Standard Deviation 1.5
|
2.0 g/L
Standard Deviation 2.8
|
1.0 g/L
Standard Deviation 1.2
|
0.5 g/L
Standard Deviation 1.3
|
0.0 g/L
Standard Deviation 0.8
|
3.5 g/L
Standard Deviation 2.1
|
0.0 g/L
Standard Deviation 0.0
|
05 g/L
Standard Deviation 1.7
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group
Baseline (pre-dose Day 1)
|
46.2 g/L
Standard Deviation 3.1
|
45.0 g/L
Standard Deviation 2.8
|
45.3 g/L
Standard Deviation 3.9
|
45.0 g/L
Standard Deviation 1.2
|
45.3 g/L
Standard Deviation 3.4
|
46.0 g/L
Standard Deviation 1.4
|
44.0 g/L
Standard Deviation 1.2
|
44.3 g/L
Standard Deviation 1.5
|
44.0 g/L
Standard Deviation 1.4
|
45.8 g/L
Standard Deviation 3.1
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group
Change from BL at 24h
|
-0.3 g/L
Standard Deviation 1.2
|
1.7 g/L
Standard Deviation 1.5
|
0.3 g/L
Standard Deviation 1.5
|
2.0 g/L
Standard Deviation 2.6
|
1.5 g/L
Standard Deviation 3.7
|
3.5 g/L
Standard Deviation 1.3
|
1.5 g/L
Standard Deviation 3.1
|
5.3 g/L
Standard Deviation 2.6
|
0.5 g/L
Standard Deviation 2.1
|
0.0 g/L
Standard Deviation 2.7
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group
Baseline (pre-dose Day 1)
|
176.0 mg/dL
Standard Deviation 47.7
|
151.0 mg/dL
Standard Deviation 26.6
|
146.3 mg/dL
Standard Deviation 37.5
|
149.0 mg/dL
Standard Deviation 38.3
|
146.5 mg/dL
Standard Deviation 49.7
|
167.5 mg/dL
Standard Deviation 42.3
|
212.8 mg/dL
Standard Deviation 48.2
|
174.5 mg/dL
Standard Deviation 34.5
|
200.5 mg/dL
Standard Deviation 10.6
|
166.5 mg/dL
Standard Deviation 28.1
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group
Change from BL at 24h
|
4.8 mg/dL
Standard Deviation 5.5
|
12.5 mg/dL
Standard Deviation 10.6
|
5.3 mg/dL
Standard Deviation 2.2
|
5.3 mg/dL
Standard Deviation 6.4
|
9.5 mg/dL
Standard Deviation 14.0
|
19.5 mg/dL
Standard Deviation 4.0
|
8.3 mg/dL
Standard Deviation 21.0
|
25.0 mg/dL
Standard Deviation 12.7
|
12.5 mg/dL
Standard Deviation 12.0
|
5.8 mg/dL
Standard Deviation 10.7
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group
Change from BL at FU
|
5.0 mg/dL
Standard Deviation 20.4
|
26.3 mg/dL
Standard Deviation 27.2
|
25.3 mg/dL
Standard Deviation 5.1
|
21.5 mg/dL
Standard Deviation 15.5
|
28.3 mg/dL
Standard Deviation 17.7
|
24.3 mg/dL
Standard Deviation 16.7
|
-13.8 mg/dL
Standard Deviation 33.7
|
6.8 mg/dL
Standard Deviation 5.4
|
-2.5 mg/dL
Standard Deviation 41.7
|
8.3 mg/dL
Standard Deviation 9.3
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group
Baseline (pre-dose Day 1)
|
50.0 mg/dL
Standard Deviation 11.1
|
49.8 mg/dL
Standard Deviation 8.4
|
45.5 mg/dL
Standard Deviation 11.0
|
49.5 mg/dL
Standard Deviation 8.9
|
40.0 mg/dL
Standard Deviation 4.1
|
54.5 mg/dL
Standard Deviation 5.5
|
51.5 mg/dL
Standard Deviation 9.6
|
48.0 mg/dL
Standard Deviation 13.3
|
47.0 mg/dL
Standard Deviation 17.0
|
45.8 mg/dL
Standard Deviation 7.3
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group
Change from BL at 24h
|
-2.8 mg/dL
Standard Deviation 2.4
|
0.5 mg/dL
Standard Deviation 3.1
|
1.0 mg/dL
Standard Deviation 1.2
|
-2.5 mg/dL
Standard Deviation 2.9
|
-1.3 mg/dL
Standard Deviation 2.1
|
2.8 mg/dL
Standard Deviation 2.2
|
-3.0 mg/dL
Standard Deviation 6.0
|
10.0 mg/dL
Standard Deviation 7.3
|
2.5 mg/dL
Standard Deviation 7.8
|
-0.3 mg/dL
Standard Deviation 1.5
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group
Change from BL at FU
|
1.8 mg/dL
Standard Deviation 5.2
|
4.5 mg/dL
Standard Deviation 5.0
|
6.3 mg/dL
Standard Deviation 4.6
|
3.0 mg/dL
Standard Deviation 3.6
|
7.3 mg/dL
Standard Deviation 2.6
|
2.8 mg/dL
Standard Deviation 5.1
|
-3.0 mg/dL
Standard Deviation 9.9
|
8.8 mg/dL
Standard Deviation 7.4
|
-2.0 mg/dL
Standard Deviation 7.1
|
1.5 mg/dL
Standard Deviation 6.1
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group
Baseline (pre-dose Day 1)
|
72.8 mg/dL
Standard Deviation 19.0
|
88.5 mg/dL
Standard Deviation 62.1
|
57.3 mg/dL
Standard Deviation 13.0
|
84.5 mg/dL
Standard Deviation 46.8
|
72.0 mg/dL
Standard Deviation 9.6
|
71.0 mg/dL
Standard Deviation 33.6
|
76.3 mg/dL
Standard Deviation 15.7
|
117.0 mg/dL
Standard Deviation 99.5
|
92.5 mg/dL
Standard Deviation 57.3
|
86.3 mg/dL
Standard Deviation 20.8
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group
Change from BL at 24h
|
16.7 mg/dL
Standard Deviation 7.2
|
19.0 mg/dL
Standard Deviation 17.3
|
10.3 mg/dL
Standard Deviation 3.0
|
31.0 mg/dL
Standard Deviation 18.1
|
20.3 mg/dL
Standard Deviation 16.3
|
22.5 mg/dL
Standard Deviation 18.4
|
27.0 mg/dL
Standard Deviation 9.5
|
-10.3 mg/dL
Standard Deviation 46.7
|
1.5 mg/dL
Standard Deviation 29.0
|
7.8 mg/dL
Standard Deviation 20.2
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group
Change from BL at FU
|
16.5 mg/dL
Standard Deviation 24.5
|
24.5 mg/dL
Standard Deviation 58.6
|
30.8 mg/dL
Standard Deviation 48.8
|
47.3 mg/dL
Standard Deviation 75.3
|
12.5 mg/dL
Standard Deviation 19.3
|
37.5 mg/dL
Standard Deviation 86.5
|
37.8 mg/dL
Standard Deviation 47.1
|
-16.5 mg/dL
Standard Deviation 48.6
|
43.5 mg/dL
Standard Deviation 89.8
|
-1.8 mg/dL
Standard Deviation 18.6
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group
Baseline (pre-dose Day 1)
|
111.1 mg/dL
Standard Deviation 41.9
|
83.5 mg/dL
Standard Deviation 24.9
|
88.9 mg/dL
Standard Deviation 32.5
|
82.5 mg/dL
Standard Deviation 35.3
|
92.3 mg/dL
Standard Deviation 46.4
|
98.7 mg/dL
Standard Deviation 35.6
|
145.9 mg/dL
Standard Deviation 45.7
|
103.1 mg/dL
Standard Deviation 40.0
|
134.5 mg/dL
Standard Deviation 16.3
|
103.5 mg/dL
Standard Deviation 25.7
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group
Change from BL at 24h
|
4.5 mg/dL
Standard Deviation 6.9
|
8.3 mg/dL
Standard Deviation 4.6
|
2.9 mg/dL
Standard Deviation 3.1
|
1.4 mg/dL
Standard Deviation 6.4
|
6.4 mg/dL
Standard Deviation 10.3
|
12.8 mg/dL
Standard Deviation 2.6
|
5.7 mg/dL
Standard Deviation 16.2
|
16.7 mg/dL
Standard Deviation 7.8
|
10.0 mg/dL
Standard Deviation 9.9
|
4.4 mg/dL
Standard Deviation 7.1
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group
Change from BL at FU
|
0.3 mg/dL
Standard Deviation 19.7
|
17.0 mg/dL
Standard Deviation 15.6
|
13.3 mg/dL
Standard Deviation 10.8
|
9.6 mg/dL
Standard Deviation 6.9
|
18.5 mg/dL
Standard Deviation 16.4
|
14.2 mg/dL
Standard Deviation 6.2
|
-17.9 mg/dL
Standard Deviation 35.8
|
1.3 mg/dL
Standard Deviation 7.7
|
-8.5 mg/dL
Standard Deviation 30.4
|
7.2 mg/dL
Standard Deviation 6.8
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group
Baseline (pre-dose Day 1)
|
25.68 mmol/L
Standard Deviation 1.38
|
25.22 mmol/L
Standard Deviation 0.51
|
24.78 mmol/L
Standard Deviation 1.09
|
25.85 mmol/L
Standard Deviation 0.53
|
24.85 mmol/L
Standard Deviation 1.21
|
24.28 mmol/L
Standard Deviation 0.33
|
27.05 mmol/L
Standard Deviation 0.91
|
26.03 mmol/L
Standard Deviation 1.80
|
24.90 mmol/L
Standard Deviation 0.71
|
25.93 mmol/L
Standard Deviation 0.84
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group
Change from BL at 24h
|
-0.05 mmol/L
Standard Deviation 1.15
|
0.28 mmol/L
Standard Deviation 1.31
|
1.05 mmol/L
Standard Deviation 1.27
|
1.18 mmol/L
Standard Deviation 0.90
|
0.40 mmol/L
Standard Deviation 0.94
|
2.35 mmol/L
Standard Deviation 0.70
|
-0.17 mmol/L
Standard Deviation 0.94
|
0.05 mmol/L
Standard Deviation 1.55
|
1.95 mmol/L
Standard Deviation 0.64
|
0.05 mmol/L
Standard Deviation 0.39
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group
Change from BL at FU
|
-1.22 mmol/L
Standard Deviation 1.38
|
0.97 mmol/L
Standard Deviation 1.04
|
-0.58 mmol/L
Standard Deviation 1.46
|
0.95 mmol/L
Standard Deviation 0.88
|
-0.15 mmol/L
Standard Deviation 0.55
|
1.65 mmol/L
Standard Deviation 1.20
|
-2.38 mmol/L
Standard Deviation 1.64
|
-0.20 mmol/L
Standard Deviation 1.03
|
-0.55 mmol/L
Standard Deviation 0.49
|
-1.23 mmol/L
Standard Deviation 0.30
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group
Baseline (pre-dose Day 1)
|
1.45 mU/L
Standard Deviation 0.56
|
1.26 mU/L
Standard Deviation 0.64
|
1.14 mU/L
Standard Deviation 0.36
|
1.14 mU/L
Standard Deviation 0.55
|
1.50 mU/L
Standard Deviation 0.97
|
1.55 mU/L
Standard Deviation 0.66
|
1.83 mU/L
Standard Deviation 0.78
|
1.59 mU/L
Standard Deviation 1.03
|
2.57 mU/L
Standard Deviation 2.31
|
1.93 mU/L
Standard Deviation 0.95
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group
Change from BL at 24h
|
-0.20 mU/L
Standard Deviation 0.09
|
0.04 mU/L
Standard Deviation 0.29
|
-0.12 mU/L
Standard Deviation 0.22
|
-0.03 mU/L
Standard Deviation 0.18
|
0.07 mU/L
Standard Deviation 0.22
|
0.46 mU/L
Standard Deviation 0.52
|
0.05 mU/L
Standard Deviation 0.35
|
-0.12 mU/L
Standard Deviation 0.25
|
-0.54 mU/L
Standard Deviation 0.65
|
-0.42 mU/L
Standard Deviation 0.42
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group
Change from BL at FU
|
0.08 mU/L
Standard Deviation 0.35
|
0.45 mU/L
Standard Deviation 1.02
|
0.10 mU/L
Standard Deviation 0.22
|
0.77 mU/L
Standard Deviation 0.92
|
0.32 mU/L
Standard Deviation 0.27
|
0.11 mU/L
Standard Deviation 0.58
|
0.17 mU/L
Standard Deviation 0.42
|
-0.06 mU/L
Standard Deviation 0.21
|
-0.69 mU/L
Standard Deviation 0.73
|
-0.10 mU/L
Standard Deviation 0.22
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group
Baseline (pre-dose Day 1)
|
1.27 ng/dL
Standard Deviation 0.14
|
1.22 ng/dL
Standard Deviation 0.16
|
1.30 ng/dL
Standard Deviation 0.14
|
1.38 ng/dL
Standard Deviation 0.17
|
1.25 ng/dL
Standard Deviation 0.10
|
1.08 ng/dL
Standard Deviation 0.05
|
1.20 ng/dL
Standard Deviation 0.14
|
1.15 ng/dL
Standard Deviation 0.06
|
1.35 ng/dL
Standard Deviation 0.07
|
1.22 ng/dL
Standard Deviation 0.17
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group
Change from BL at 24h
|
-0.05 ng/dL
Standard Deviation 0.08
|
0.03 ng/dL
Standard Deviation 0.05
|
-0.08 ng/dL
Standard Deviation 0.10
|
-0.08 ng/dL
Standard Deviation 0.10
|
-0.05 ng/dL
Standard Deviation 0.06
|
0.12 ng/dL
Standard Deviation 0.05
|
0.05 ng/dL
Standard Deviation 0.13
|
0.10 ng/dL
Standard Deviation 0.08
|
0.05 ng/dL
Standard Deviation 0.07
|
0.03 ng/dL
Standard Deviation 0.13
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group
Change from BL at FU
|
0.03 ng/dL
Standard Deviation 0.10
|
0.15 ng/dL
Standard Deviation 0.10
|
0.02 ng/dL
Standard Deviation 0.22
|
0.05 ng/dL
Standard Deviation 0.06
|
0.07 ng/dL
Standard Deviation 0.05
|
0.22 ng/dL
Standard Deviation 0.05
|
0.05 ng/dL
Standard Deviation 0.10
|
0.13 ng/dL
Standard Deviation 0.05
|
-0.10 ng/dL
Standard Deviation 0.14
|
0.10 ng/dL
Standard Deviation 0.08
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group
Change from BL at 24h
|
-0.80 mg/dL
Standard Deviation 1.83
|
1.40 mg/dL
Standard Deviation 2.82
|
-2.08 mg/dL
Standard Deviation 2.41
|
2.10 mg/dL
Standard Deviation 3.81
|
-0.50 mg/dL
Standard Deviation 1.67
|
0.88 mg/dL
Standard Deviation 3.62
|
0.78 mg/dL
Standard Deviation 1.75
|
3.25 mg/dL
Standard Deviation 1.54
|
-1.05 mg/dL
Standard Deviation 0.07
|
0.40 mg/dL
Standard Deviation 2.22
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group
Change from BL at FU
|
1.05 mg/dL
Standard Deviation 4.59
|
3.80 mg/dL
Standard Deviation 3.12
|
2.25 mg/dL
Standard Deviation 5.84
|
3.45 mg/dL
Standard Deviation 3.45
|
1.93 mg/dL
Standard Deviation 6.23
|
0.70 mg/dL
Standard Deviation 2.45
|
-0.02 mg/dL
Standard Deviation 3.40
|
4.33 mg/dL
Standard Deviation 3.08
|
-0.15 mg/dL
Standard Deviation 0.64
|
1.70 mg/dL
Standard Deviation 4.59
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group
Baseline (pre-dose Day 1)
|
7.98 mg/dL
Standard Deviation 2.47
|
7.28 mg/dL
Standard Deviation 1.86
|
8.65 mg/dL
Standard Deviation 3.20
|
8.23 mg/dL
Standard Deviation 2.04
|
8.10 mg/dL
Standard Deviation 2.93
|
9.03 mg/dL
Standard Deviation 2.08
|
7.53 mg/dL
Standard Deviation 0.97
|
8.58 mg/dL
Standard Deviation 2.68
|
9.85 mg/dL
Standard Deviation 1.34
|
8.33 mg/dL
Standard Deviation 1.50
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group
Baseline (pre-dose Day 1)
|
65.3 g/L
Standard Deviation 3.8
|
67.3 g/L
Standard Deviation 4.6
|
63.8 g/L
Standard Deviation 1.3
|
66.0 g/L
Standard Deviation 2.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group
Change from BL at Day 3
|
4.0 g/L
Standard Deviation 2.4
|
2.3 g/L
Standard Deviation 1.7
|
2.5 g/L
Standard Deviation 1.7
|
1.7 g/L
Standard Deviation 2.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group
Change from BL at Day 8
|
7.0 g/L
Standard Deviation 2.9
|
4.3 g/L
Standard Deviation 4.3
|
6.0 g/L
Standard Deviation 4.1
|
4.8 g/L
Standard Deviation 1.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group
Change from BL at FU
|
5.0 g/L
Standard Deviation 3.4
|
4.8 g/L
Standard Deviation 4.1
|
4.0 g/L
Standard Deviation 2.9
|
1.8 g/L
Standard Deviation 2.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group
Baseline (pre-dose Day 1)
|
66.0 U/L
Standard Deviation 16.1
|
67.3 U/L
Standard Deviation 10.7
|
55.3 U/L
Standard Deviation 7.3
|
52.3 U/L
Standard Deviation 9.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group
Change from BL at Day 3
|
7.3 U/L
Standard Deviation 6.7
|
2.0 U/L
Standard Deviation 1.4
|
1.5 U/L
Standard Deviation 3.9
|
1.8 U/L
Standard Deviation 1.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group
Change from BL at Day 8
|
13.0 U/L
Standard Deviation 9.7
|
5.0 U/L
Standard Deviation 4.2
|
6.0 U/L
Standard Deviation 6.4
|
3.3 U/L
Standard Deviation 1.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group
Change from BL at FU
|
9.0 U/L
Standard Deviation 13.3
|
10.8 U/L
Standard Deviation 4.6
|
9.8 U/L
Standard Deviation 5.2
|
3.3 U/L
Standard Deviation 4.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group
Baseline (pre-dose Day 1)
|
20.3 U/L
Standard Deviation 3.8
|
21.5 U/L
Standard Deviation 5.7
|
18.5 U/L
Standard Deviation 0.6
|
23.0 U/L
Standard Deviation 6.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group
Change from BL at Day 3
|
-2.0 U/L
Standard Deviation 4.2
|
-5.0 U/L
Standard Deviation 1.4
|
-2.5 U/L
Standard Deviation 1.3
|
-1.7 U/L
Standard Deviation 3.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group
Change from BL at Day 8
|
-1.0 U/L
Standard Deviation 6.1
|
-2.8 U/L
Standard Deviation 1.9
|
-0.3 U/L
Standard Deviation 2.8
|
-1.5 U/L
Standard Deviation 4.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group
Change from BL at FU
|
1.5 U/L
Standard Deviation 3.9
|
1.3 U/L
Standard Deviation 4.6
|
9.8 U/L
Standard Deviation 16.3
|
2.8 U/L
Standard Deviation 8.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group
Baseline (pre-dose Day 1)
|
129.5 U/L
Standard Deviation 62.0
|
192.3 U/L
Standard Deviation 149.4
|
146.5 U/L
Standard Deviation 70.8
|
229.8 U/L
Standard Deviation 156.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group
Change from BL at Day 3
|
-48.5 U/L
Standard Deviation 40.7
|
-68.8 U/L
Standard Deviation 57.3
|
-58.0 U/L
Standard Deviation 53.3
|
-106.5 U/L
Standard Deviation 115.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group
Change from BL at Day 8
|
-50.8 U/L
Standard Deviation 49.4
|
-83.8 U/L
Standard Deviation 91.7
|
-68.0 U/L
Standard Deviation 57.7
|
-123.5 U/L
Standard Deviation 144.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group
Change from BL at FU
|
27.0 U/L
Standard Deviation 23.1
|
-7.5 U/L
Standard Deviation 81.2
|
150.5 U/L
Standard Deviation 313.3
|
42.2 U/L
Standard Deviation 153.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group
Baseline (pre-dose Day 1)
|
15.5 U/L
Standard Deviation 7.0
|
18.3 U/L
Standard Deviation 9.2
|
20.5 U/L
Standard Deviation 14.5
|
21.5 U/L
Standard Deviation 11.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group
Change from BL at Day 3
|
0.5 U/L
Standard Deviation 1.0
|
0.3 U/L
Standard Deviation 1.3
|
2.0 U/L
Standard Deviation 2.2
|
0.7 U/L
Standard Deviation 1.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group
Change from BL at Day 8
|
0.8 U/L
Standard Deviation 1.9
|
0.3 U/L
Standard Deviation 3.0
|
1.8 U/L
Standard Deviation 2.8
|
0.0 U/L
Standard Deviation 2.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group
Change from BL at FU
|
1.3 U/L
Standard Deviation 1.3
|
-0.5 U/L
Standard Deviation 3.1
|
1.8 U/L
Standard Deviation 2.2
|
-0.8 U/L
Standard Deviation 2.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group
Baseline (pre-dose Day 1)
|
0.50 mg/dL
Standard Deviation 0.47
|
0.55 mg/dL
Standard Deviation 0.13
|
0.63 mg/dL
Standard Deviation 0.15
|
0.65 mg/dL
Standard Deviation 0.29
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group
Change from BL at Day 3
|
0.38 mg/dL
Standard Deviation 0.22
|
0.05 mg/dL
Standard Deviation 0.13
|
0.20 mg/dL
Standard Deviation 0.16
|
0.13 mg/dL
Standard Deviation 0.08
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group
Change from BL at Day 8
|
0.33 mg/dL
Standard Deviation 0.26
|
0.03 mg/dL
Standard Deviation 0.21
|
0.18 mg/dL
Standard Deviation 0.25
|
0.08 mg/dL
Standard Deviation 0.08
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group
Change from BL at FU
|
-0.02 mg/dL
Standard Deviation 0.32
|
-0.08 mg/dL
Standard Deviation 0.21
|
0.08 mg/dL
Standard Deviation 0.22
|
-0.05 mg/dL
Standard Deviation 0.19
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group
Change from BL at Day 8
|
5.8 mg/dL
Standard Deviation 6.9
|
-0.5 mg/dL
Standard Deviation 3.1
|
0.5 mg/dL
Standard Deviation 1.3
|
-1.0 mg/dL
Standard Deviation 4.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group
Change from BL at FU
|
2.3 mg/dL
Standard Deviation 8.4
|
-0.5 mg/dL
Standard Deviation 6.8
|
-0.5 mg/dL
Standard Deviation 7.1
|
-0.3 mg/dL
Standard Deviation 6.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group
Baseline (pre-dose Day 1)
|
24.8 mg/dL
Standard Deviation 3.9
|
28.0 mg/dL
Standard Deviation 5.5
|
29.8 mg/dL
Standard Deviation 5.1
|
30.2 mg/dL
Standard Deviation 3.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group
Change from BL at Day 3
|
6.0 mg/dL
Standard Deviation 2.2
|
2.8 mg/dL
Standard Deviation 2.4
|
2.0 mg/dL
Standard Deviation 2.6
|
2.5 mg/dL
Standard Deviation 3.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group
Change from BL at Day 3
|
0.095 mg/dL
Standard Deviation 0.025
|
0.122 mg/dL
Standard Deviation 0.033
|
0.165 mg/dL
Standard Deviation 0.031
|
0.057 mg/dL
Standard Deviation 0.050
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group
Change from BL at FU
|
0.008 mg/dL
Standard Deviation 0.130
|
-0.020 mg/dL
Standard Deviation 0.024
|
0.017 mg/dL
Standard Deviation 0.043
|
0.007 mg/dL
Standard Deviation 0.039
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group
Baseline (pre-dose Day 1)
|
0.910 mg/dL
Standard Deviation 0.042
|
0.960 mg/dL
Standard Deviation 0.079
|
0.913 mg/dL
Standard Deviation 0.067
|
0.897 mg/dL
Standard Deviation 0.110
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group
Change from BL at Day 8
|
0.005 mg/dL
Standard Deviation 0.247
|
0.122 mg/dL
Standard Deviation 0.069
|
0.133 mg/dL
Standard Deviation 0.082
|
0.053 mg/dL
Standard Deviation 0.056
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group
Baseline (pre-dose Day 1)
|
143.8 mmol/L
Standard Deviation 1.0
|
141.3 mmol/L
Standard Deviation 0.5
|
141.0 mmol/L
Standard Deviation 1.4
|
142.0 mmol/L
Standard Deviation 0.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group
Change from BL at Day 3
|
-0.5 mmol/L
Standard Deviation 0.6
|
-1.5 mmol/L
Standard Deviation 0.6
|
0.8 mmol/L
Standard Deviation 0.5
|
-1.0 mmol/L
Standard Deviation 0.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group
Change from BL at Day 8
|
-3.0 mmol/L
Standard Deviation 0.8
|
0.8 mmol/L
Standard Deviation 0.5
|
1.0 mmol/L
Standard Deviation 0.8
|
-0.5 mmol/L
Standard Deviation 1.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group
Change from BL at FU
|
-1.5 mmol/L
Standard Deviation 1.0
|
-0.3 mmol/L
Standard Deviation 2.2
|
2.0 mmol/L
Standard Deviation 2.2
|
0.2 mmol/L
Standard Deviation 2.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group
Baseline (pre-dose Day 1)
|
4.20 mmol/L
Standard Deviation 0.08
|
4.35 mmol/L
Standard Deviation 0.19
|
4.40 mmol/L
Standard Deviation 0.40
|
4.32 mmol/L
Standard Deviation 0.17
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group
Change from BL at Day 3
|
0.45 mmol/L
Standard Deviation 0.19
|
0.33 mmol/L
Standard Deviation 0.37
|
0.10 mmol/L
Standard Deviation 0.29
|
0.52 mmol/L
Standard Deviation 0.49
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group
Change from BL at Day 8
|
0.07 mmol/L
Standard Deviation 0.30
|
0.15 mmol/L
Standard Deviation 0.39
|
0.25 mmol/L
Standard Deviation 0.42
|
0.15 mmol/L
Standard Deviation 0.41
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group
Change from BL at FU
|
0.25 mmol/L
Standard Deviation 0.39
|
0.45 mmol/L
Standard Deviation 0.31
|
0.25 mmol/L
Standard Deviation 0.59
|
0.30 mmol/L
Standard Deviation 0.26
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group
Change from BL at Day 3
|
-2.5 mmol/L
Standard Deviation 0.6
|
-2.0 mmol/L
Standard Deviation 1.8
|
-1.5 mmol/L
Standard Deviation 0.6
|
-1.5 mmol/L
Standard Deviation 0.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group
Change from BL at Day 8
|
-3.5 mmol/L
Standard Deviation 1.0
|
-2.0 mmol/L
Standard Deviation 1.4
|
-2.8 mmol/L
Standard Deviation 1.0
|
-2.2 mmol/L
Standard Deviation 2.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group
Change from BL at FU
|
-2.0 mmol/L
Standard Deviation 0.0
|
-2.3 mmol/L
Standard Deviation 1.9
|
-2.0 mmol/L
Standard Deviation 0.8
|
-1.3 mmol/L
Standard Deviation 1.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group
Baseline (pre-dose Day 1)
|
103.8 mmol/L
Standard Deviation 2.2
|
101.5 mmol/L
Standard Deviation 0.6
|
102.0 mmol/L
Standard Deviation 1.8
|
102.2 mmol/L
Standard Deviation 1.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group
Baseline (pre-dose Day 1)
|
2.278 mmol/L
Standard Deviation 0.117
|
2.310 mmol/L
Standard Deviation 0.058
|
2.265 mmol/L
Standard Deviation 0.024
|
2.323 mmol/L
Standard Deviation 0.039
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group
Change from BL at Day 3
|
0.105 mmol/L
Standard Deviation 0.051
|
0.083 mmol/L
Standard Deviation 0.067
|
0.048 mmol/L
Standard Deviation 0.068
|
0.068 mmol/L
Standard Deviation 0.046
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group
Change from BL at Day 8
|
0.127 mmol/L
Standard Deviation 0.091
|
0.083 mmol/L
Standard Deviation 0.063
|
0.100 mmol/L
Standard Deviation 0.095
|
0.088 mmol/L
Standard Deviation 0.037
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group
Change from BL at FU
|
0.087 mmol/L
Standard Deviation 0.088
|
0.083 mmol/L
Standard Deviation 0.075
|
0.045 mmol/L
Standard Deviation 0.082
|
0.055 mmol/L
Standard Deviation 0.037
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group
Change from BL at FU
|
0.08 mg/dL
Standard Deviation 0.92
|
0.55 mg/dL
Standard Deviation 0.52
|
0.22 mg/dL
Standard Deviation 0.81
|
-0.05 mg/dL
Standard Deviation 0.42
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group
Baseline (pre-dose Day 1)
|
5.65 mg/dL
Standard Deviation 1.67
|
4.93 mg/dL
Standard Deviation 0.91
|
5.40 mg/dL
Standard Deviation 0.80
|
5.25 mg/dL
Standard Deviation 1.14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group
Change from BL at Day 3
|
0.50 mg/dL
Standard Deviation 0.56
|
0.58 mg/dL
Standard Deviation 0.39
|
0.75 mg/dL
Standard Deviation 0.62
|
-0.07 mg/dL
Standard Deviation 0.31
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group
Change from BL at Day 8
|
0.28 mg/dL
Standard Deviation 1.14
|
-0.02 mg/dL
Standard Deviation 0.43
|
0.15 mg/dL
Standard Deviation 0.58
|
-0.63 mg/dL
Standard Deviation 0.52
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group
Change from BL at Day 3
|
-1.8 U/L
Standard Deviation 3.1
|
0.0 U/L
Standard Deviation 1.8
|
26.0 U/L
Standard Deviation 55.4
|
1.2 U/L
Standard Deviation 4.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group
Baseline (pre-dose Day 1)
|
26.5 U/L
Standard Deviation 6.1
|
26.5 U/L
Standard Deviation 3.3
|
32.8 U/L
Standard Deviation 12.1
|
34.2 U/L
Standard Deviation 10.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group
Change from BL at Day 8
|
-0.3 U/L
Standard Deviation 4.1
|
1.3 U/L
Standard Deviation 7.4
|
50.5 U/L
Standard Deviation 106.4
|
1.0 U/L
Standard Deviation 5.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group
Change from BL at FU
|
3.5 U/L
Standard Deviation 3.3
|
17.3 U/L
Standard Deviation 24.4
|
-2.8 U/L
Standard Deviation 7.4
|
-1.8 U/L
Standard Deviation 7.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group
Change from BL at Day 3
|
0.0 U/L
Standard Deviation 5.9
|
-0.3 U/L
Standard Deviation 2.2
|
-1.3 U/L
Standard Deviation 0.5
|
2.0 U/L
Standard Deviation 4.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group
Change from BL at Day 8
|
-1.8 U/L
Standard Deviation 12.9
|
2.3 U/L
Standard Deviation 2.6
|
0.3 U/L
Standard Deviation 5.4
|
2.8 U/L
Standard Deviation 5.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group
Baseline (pre-dose Day 1)
|
25.3 U/L
Standard Deviation 9.7
|
21.3 U/L
Standard Deviation 17.4
|
20.5 U/L
Standard Deviation 6.8
|
22.3 U/L
Standard Deviation 5.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group
Change from BL at FU
|
1.3 U/L
Standard Deviation 11.4
|
6.3 U/L
Standard Deviation 8.3
|
4.8 U/L
Standard Deviation 7.9
|
2.3 U/L
Standard Deviation 6.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group
Change from BL at Day 8
|
0.052 mmol/L
Standard Deviation 0.116
|
0.000 mmol/L
Standard Deviation 0.085
|
-0.020 mmol/L
Standard Deviation 0.068
|
-0.002 mmol/L
Standard Deviation 0.113
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group
Change from BL at FU
|
-0.030 mmol/L
Standard Deviation 0.131
|
-0.010 mmol/L
Standard Deviation 0.034
|
0.053 mmol/L
Standard Deviation 0.189
|
-0.002 mmol/L
Standard Deviation 0.190
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group
Baseline (pre-dose Day 1)
|
0.978 mmol/L
Standard Deviation 0.094
|
1.033 mmol/L
Standard Deviation 0.164
|
0.920 mmol/L
Standard Deviation 0.121
|
1.000 mmol/L
Standard Deviation 0.162
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group
Change from BL at Day 3
|
0.102 mmol/L
Standard Deviation 0.033
|
0.003 mmol/L
Standard Deviation 0.074
|
0.015 mmol/L
Standard Deviation 0.073
|
-0.005 mmol/L
Standard Deviation 0.111
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group
Change from BL at FU
|
2.8 g/L
Standard Deviation 2.1
|
3.0 g/L
Standard Deviation 2.4
|
3.3 g/L
Standard Deviation 2.1
|
1.7 g/L
Standard Deviation 1.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group
Change from BL at Day 3
|
3.3 g/L
Standard Deviation 2.2
|
3.8 g/L
Standard Deviation 1.3
|
1.3 g/L
Standard Deviation 1.0
|
1.5 g/L
Standard Deviation 2.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group
Baseline (pre-dose Day 1)
|
43.3 g/L
Standard Deviation 2.2
|
45.5 g/L
Standard Deviation 3.1
|
42.8 g/L
Standard Deviation 0.5
|
44.7 g/L
Standard Deviation 1.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group
Change from BL at Day 8
|
5.3 g/L
Standard Deviation 2.6
|
3.5 g/L
Standard Deviation 3.0
|
4.0 g/L
Standard Deviation 1.8
|
3.8 g/L
Standard Deviation 1.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group
Change from BL at Day 3
|
-6.8 mg/dL
Standard Deviation 4.5
|
2.8 mg/dL
Standard Deviation 6.3
|
-6.8 mg/dL
Standard Deviation 7.9
|
1.5 mg/dL
Standard Deviation 2.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group
Change from BL at Day 8
|
-6.5 mg/dL
Standard Deviation 7.0
|
-9.5 mg/dL
Standard Deviation 5.5
|
-7.0 mg/dL
Standard Deviation 6.1
|
-3.5 mg/dL
Standard Deviation 7.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group
Baseline (pre-dose Day 1)
|
89.0 mg/dL
Standard Deviation 5.4
|
85.5 mg/dL
Standard Deviation 13.8
|
89.8 mg/dL
Standard Deviation 7.5
|
87.2 mg/dL
Standard Deviation 10.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group
Change from BL at FU
|
-2.2 mg/dL
Standard Deviation 1.4
|
2.0 mg/dL
Standard Deviation 5.7
|
-10.8 mg/dL
Standard Deviation 7.8
|
0.0 mg/dL
Standard Deviation 7.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group
Change from BL at Day 3
|
20.0 mg/dL
Standard Deviation 11.5
|
8.8 mg/dL
Standard Deviation 9.7
|
13.5 mg/dL
Standard Deviation 4.0
|
19.7 mg/dL
Standard Deviation 15.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group
Change from BL at Day 8
|
32.3 mg/dL
Standard Deviation 25.3
|
2.5 mg/dL
Standard Deviation 20.5
|
13.3 mg/dL
Standard Deviation 17.7
|
24.3 mg/dL
Standard Deviation 24.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group
Change from BL at FU
|
9.3 mg/dL
Standard Deviation 14.2
|
8.0 mg/dL
Standard Deviation 22.2
|
9.8 mg/dL
Standard Deviation 17.8
|
-5.5 mg/dL
Standard Deviation 8.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group
Baseline (pre-dose Day 1)
|
192.8 mg/dL
Standard Deviation 33.5
|
191.0 mg/dL
Standard Deviation 11.3
|
203.5 mg/dL
Standard Deviation 7.4
|
177.8 mg/dL
Standard Deviation 30.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group
Change from BL at Day 8
|
17.8 mg/dL
Standard Deviation 44.2
|
46.8 mg/dL
Standard Deviation 26.9
|
69.0 mg/dL
Standard Deviation 42.1
|
28.3 mg/dL
Standard Deviation 18.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group
Change from BL at FU
|
16.0 mg/dL
Standard Deviation 52.1
|
0.5 mg/dL
Standard Deviation 33.5
|
20.3 mg/dL
Standard Deviation 56.6
|
-8.0 mg/dL
Standard Deviation 39.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group
Baseline (pre-dose Day 1)
|
140.3 mg/dL
Standard Deviation 77.7
|
83.5 mg/dL
Standard Deviation 26.3
|
114.0 mg/dL
Standard Deviation 74.6
|
90.2 mg/dL
Standard Deviation 67.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group
Change from BL at Day 3
|
14.8 mg/dL
Standard Deviation 32.2
|
35.5 mg/dL
Standard Deviation 32.7
|
30.5 mg/dL
Standard Deviation 30.0
|
14.8 mg/dL
Standard Deviation 29.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group
Baseline (pre-dose Day 1)
|
114.1 mg/dL
Standard Deviation 32.7
|
112.9 mg/dL
Standard Deviation 19.0
|
127.0 mg/dL
Standard Deviation 18.1
|
93.3 mg/dL
Standard Deviation 23.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group
Change from BL at Day 3
|
17.9 mg/dL
Standard Deviation 14.5
|
4.9 mg/dL
Standard Deviation 5.2
|
9.0 mg/dL
Standard Deviation 7.9
|
18.8 mg/dL
Standard Deviation 13.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group
Change from BL at Day 8
|
33.2 mg/dL
Standard Deviation 32.8
|
1.4 mg/dL
Standard Deviation 13.8
|
3.5 mg/dL
Standard Deviation 20.0
|
25.6 mg/dL
Standard Deviation 25.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group
Change from BL at FU
|
8.1 mg/dL
Standard Deviation 11.0
|
6.9 mg/dL
Standard Deviation 9.6
|
-1.5 mg/dL
Standard Deviation 20.7
|
-1.9 mg/dL
Standard Deviation 9.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group
Change from BL at Day 8
|
-5.0 mg/dL
Standard Deviation 6.1
|
-7.8 mg/dL
Standard Deviation 8.6
|
-3.5 mg/dL
Standard Deviation 11.2
|
-7.0 mg/dL
Standard Deviation 6.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group
Baseline (pre-dose Day 1)
|
51.0 mg/dL
Standard Deviation 15.1
|
61.0 mg/dL
Standard Deviation 20.1
|
53.5 mg/dL
Standard Deviation 20.5
|
66.8 mg/dL
Standard Deviation 17.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group
Change from BL at Day 3
|
-1.0 mg/dL
Standard Deviation 5.7
|
-3.0 mg/dL
Standard Deviation 4.8
|
-1.5 mg/dL
Standard Deviation 5.8
|
-2.5 mg/dL
Standard Deviation 6.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group
Change from BL at FU
|
-2.5 mg/dL
Standard Deviation 2.1
|
1.3 mg/dL
Standard Deviation 9.9
|
7.5 mg/dL
Standard Deviation 12.1
|
-2.2 mg/dL
Standard Deviation 8.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group
Change from BL at Day 3
|
0.11 mU/L
Standard Deviation 0.33
|
0.09 mU/L
Standard Deviation 0.21
|
0.48 mU/L
Standard Deviation 0.54
|
0.25 mU/L
Standard Deviation 0.39
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group
Baseline (pre-dose Day 1)
|
1.41 mU/L
Standard Deviation 0.78
|
1.48 mU/L
Standard Deviation 0.45
|
1.20 mU/L
Standard Deviation 0.36
|
1.58 mU/L
Standard Deviation 0.41
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group
Change from BL at Day 8
|
0.28 mU/L
Standard Deviation 0.35
|
0.45 mU/L
Standard Deviation 0.23
|
0.75 mU/L
Standard Deviation 0.52
|
0.85 mU/L
Standard Deviation 0.54
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group
Change from BL at FU
|
0.16 mU/L
Standard Deviation 0.50
|
-0.15 mU/L
Standard Deviation 0.29
|
0.05 mU/L
Standard Deviation 0.48
|
0.05 mU/L
Standard Deviation 0.39
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=44 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group
Baseline (pre-dose Day 1)
|
3.35 pg/mL
Standard Deviation 0.58
|
3.35 pg/mL
Standard Deviation 0.26
|
3.30 pg/mL
Standard Deviation 0.14
|
3.08 pg/mL
Standard Deviation 0.35
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group
Change from BL at Day 3
|
-0.05 pg/mL
Standard Deviation 0.19
|
-0.28 pg/mL
Standard Deviation 0.29
|
-0.15 pg/mL
Standard Deviation 0.19
|
-0.15 pg/mL
Standard Deviation 0.34
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group
Change from BL at Day 8
|
-0.32 pg/mL
Standard Deviation 0.30
|
0.10 pg/mL
Standard Deviation 0.27
|
-0.13 pg/mL
Standard Deviation 0.22
|
-0.05 pg/mL
Standard Deviation 0.33
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group
Change from BL at FU
|
0.30 pg/mL
Standard Deviation 0.26
|
-0.05 pg/mL
Standard Deviation 0.30
|
0.18 pg/mL
Standard Deviation 0.29
|
0.18 pg/mL
Standard Deviation 0.08
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group
Baseline (pre-dose Day 1)
|
1.20 ng/dL
Standard Deviation 0.08
|
1.25 ng/dL
Standard Deviation 0.06
|
1.20 ng/dL
Standard Deviation 0.18
|
1.07 ng/dL
Standard Deviation 0.14
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group
Change from BL at Day 3
|
0.05 ng/dL
Standard Deviation 0.06
|
0.02 ng/dL
Standard Deviation 0.05
|
0.05 ng/dL
Standard Deviation 0.06
|
0.03 ng/dL
Standard Deviation 0.08
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group
Change from BL at Day 8
|
0.12 ng/dL
Standard Deviation 0.05
|
0.07 ng/dL
Standard Deviation 0.10
|
0.23 ng/dL
Standard Deviation 0.10
|
0.17 ng/dL
Standard Deviation 0.10
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group
Change from BL at FU
|
0.12 ng/dL
Standard Deviation 0.05
|
0.03 ng/dL
Standard Deviation 0.10
|
0.12 ng/dL
Standard Deviation 0.05
|
0.10 ng/dL
Standard Deviation 0.06
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group
Baseline (pre-dose Day 1)
|
27.53 mmol/L
Standard Deviation 0.54
|
25.53 mmol/L
Standard Deviation 0.92
|
28.53 mmol/L
Standard Deviation 0.59
|
27.23 mmol/L
Standard Deviation 0.87
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group
Change from BL at Day 3
|
-0.38 mmol/L
Standard Deviation 0.79
|
2.20 mmol/L
Standard Deviation 1.51
|
0.10 mmol/L
Standard Deviation 1.55
|
0.03 mmol/L
Standard Deviation 1.40
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group
Change from BL at Day 8
|
-1.10 mmol/L
Standard Deviation 1.62
|
1.42 mmol/L
Standard Deviation 1.59
|
-0.55 mmol/L
Standard Deviation 1.72
|
0.47 mmol/L
Standard Deviation 1.69
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group
Change from BL at FU
|
-1.18 mmol/L
Standard Deviation 0.69
|
1.68 mmol/L
Standard Deviation 1.27
|
-0.32 mmol/L
Standard Deviation 1.78
|
-0.27 mmol/L
Standard Deviation 1.87
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline, Day 3, Day 8, FU (one week after last dosing)Population: The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176.
Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group
Baseline (pre-dose Day 1)
|
8.63 mg/dL
Standard Deviation 4.26
|
7.00 mg/dL
Standard Deviation 1.82
|
7.23 mg/dL
Standard Deviation 1.08
|
9.12 mg/dL
Standard Deviation 1.94
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group
Change from BL at Day 3
|
0.98 mg/dL
Standard Deviation 1.06
|
2.23 mg/dL
Standard Deviation 4.01
|
1.18 mg/dL
Standard Deviation 1.41
|
5.93 mg/dL
Standard Deviation 6.62
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group
Change from BL at Day 8
|
3.13 mg/dL
Standard Deviation 3.00
|
2.30 mg/dL
Standard Deviation 2.08
|
1.83 mg/dL
Standard Deviation 1.56
|
1.23 mg/dL
Standard Deviation 3.66
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group
Change from BL at FU
|
2.75 mg/dL
Standard Deviation 3.30
|
1.08 mg/dL
Standard Deviation 1.49
|
6.63 mg/dL
Standard Deviation 4.95
|
-0.12 mg/dL
Standard Deviation 4.07
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1, Day 7Population: Per protocol set
Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Phospholipidosis
Normalized di-22:6-BMP: Change from Day 1 to Day 7
|
1.298 ng/mL
Standard Deviation 0.819
|
0.060 ng/mL
Standard Deviation 1.152
|
0.337 ng/mL
Standard Deviation 1.120
|
1.780 ng/mL
Standard Deviation 1.874
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Phospholipidosis
di-22:6-BMP: Change from Day 1 to Day 7
|
-1.473 ng/mL
Standard Deviation 4.520
|
-3.465 ng/mL
Standard Deviation 4.870
|
-2.630 ng/mL
Standard Deviation 2.633
|
-1.592 ng/mL
Standard Deviation 3.283
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-upPopulation: Safety Analysis Set
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Baseline (Pre-dose Day 1)
|
391.3 msec
Standard Deviation 10.8
|
381.0 msec
Standard Deviation 28.9
|
384.0 msec
Standard Deviation 11.0
|
385.2 msec
Standard Deviation 15.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from BL at pre-dose Day 6
|
5.5 msec
Standard Deviation 9.9
|
-2.3 msec
Standard Deviation 6.7
|
13.5 msec
Standard Deviation 13.8
|
-10.5 msec
Standard Deviation 14.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from BL at pre-dose Day 7
|
7.0 msec
Standard Deviation 6.5
|
5.5 msec
Standard Deviation 9.6
|
18.0 msec
Standard Deviation 9.2
|
-11.3 msec
Standard Deviation 7.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from BL at FU
|
7.8 msec
Standard Deviation 9.7
|
11.0 msec
Standard Deviation 3.2
|
10.5 msec
Standard Deviation 24.4
|
3.8 msec
Standard Deviation 14.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from baseline at 2h - Day 1
|
3.8 msec
Standard Deviation 10.3
|
12.3 msec
Standard Deviation 8.8
|
11.8 msec
Standard Deviation 9.7
|
0.7 msec
Standard Deviation 6.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from BL at 24h - Day 1
|
-1.0 msec
Standard Deviation 9.8
|
0.3 msec
Standard Deviation 6.2
|
11.5 msec
Standard Deviation 19.2
|
-5.7 msec
Standard Deviation 9.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Baseline (pre-dose Day 7)
|
398.3 msec
Standard Deviation 7.9
|
386.5 msec
Standard Deviation 26.1
|
402.0 msec
Standard Deviation 6.6
|
378.8 msec
Standard Deviation 13.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from pre-dose Day 7 at 1h - Day 7
|
-3.8 msec
Standard Deviation 9.1
|
-3.8 msec
Standard Deviation 7.9
|
-10.3 msec
Standard Deviation 11.1
|
-3.5 msec
Standard Deviation 6.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from pre-dose Day 7 at 2h - Day 7
|
-5.0 msec
Standard Deviation 4.2
|
5.8 msec
Standard Deviation 15.2
|
2.5 msec
Standard Deviation 8.7
|
1.0 msec
Standard Deviation 16.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from pre-dose Day 7 at 4h
|
-7.8 msec
Standard Deviation 7.7
|
-3.8 msec
Standard Deviation 6.2
|
-6.5 msec
Standard Deviation 13.9
|
-0.5 msec
Standard Deviation 12.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from pre-dose Day 7 BL at 6h - Day 7
|
5.3 msec
Standard Deviation 9.8
|
12.5 msec
Standard Deviation 7.0
|
-1.8 msec
Standard Deviation 8.3
|
5.8 msec
Standard Deviation 23.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from pre-dose Day 7 at 8h - Day 7
|
-7.0 msec
Standard Deviation 2.8
|
-4.5 msec
Standard Deviation 9.7
|
-11.5 msec
Standard Deviation 7.2
|
3.0 msec
Standard Deviation 6.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from pre-dose Day 7 at 12h - Day 7
|
4.5 msec
Standard Deviation 11.4
|
3.0 msec
Standard Deviation 5.0
|
-9.0 msec
Standard Deviation 8.1
|
6.7 msec
Standard Deviation 5.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from BL at pre-dose Day 2
|
-1.0 msec
Standard Deviation 9.8
|
0.3 msec
Standard Deviation 6.2
|
11.5 msec
Standard Deviation 19.2
|
-5.7 msec
Standard Deviation 9.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from BL at pre-dose Day 3
|
6.0 msec
Standard Deviation 14.1
|
0.5 msec
Standard Deviation 9.7
|
20.5 msec
Standard Deviation 22.3
|
-8.5 msec
Standard Deviation 5.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from BL at pre-dose Day 4
|
6.5 msec
Standard Deviation 11.5
|
2.0 msec
Standard Deviation 14.7
|
7.5 msec
Standard Deviation 17.1
|
-10.2 msec
Standard Deviation 5.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB)
Change from BL at pre-dose Day 5
|
13.8 msec
Standard Deviation 14.3
|
10.3 msec
Standard Deviation 4.3
|
14.0 msec
Standard Deviation 14.2
|
-8.5 msec
Standard Deviation 5.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-upThe baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Baseline (Pre-dose Day 1)
|
185.8 msec
Standard Deviation 33.4
|
160.5 msec
Standard Deviation 18.5
|
162.0 msec
Standard Deviation 7.0
|
171.8 msec
Standard Deviation 20.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from baseline at 2h - Day 1
|
2.8 msec
Standard Deviation 2.8
|
-1.5 msec
Standard Deviation 3.0
|
6.0 msec
Standard Deviation 5.0
|
6.2 msec
Standard Deviation 10.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from BL at pre-dose Day 7
|
5.8 msec
Standard Deviation 6.8
|
3.5 msec
Standard Deviation 5.7
|
5.5 msec
Standard Deviation 5.7
|
6.5 msec
Standard Deviation 20.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from BL at FU
|
-6.8 msec
Standard Deviation 12.0
|
-2.5 msec
Standard Deviation 3.4
|
-3.5 msec
Standard Deviation 6.4
|
0.5 msec
Standard Deviation 16.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from BL at 24h - Day 1
|
-5.8 msec
Standard Deviation 6.1
|
-0.5 msec
Standard Deviation 1.9
|
2.0 msec
Standard Deviation 6.6
|
-6.5 msec
Standard Deviation 14.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Baseline (pre-dose Day 7)
|
191.5 msec
Standard Deviation 33.4
|
164.0 msec
Standard Deviation 22.9
|
167.5 msec
Standard Deviation 5.3
|
178.3 msec
Standard Deviation 11.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from pre-dose Day 7 at 1h - Day 7
|
-1.0 msec
Standard Deviation 4.8
|
5.5 msec
Standard Deviation 30
|
6.5 msec
Standard Deviation 2.5
|
-1.7 msec
Standard Deviation 2.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from pre-dose Day 7 at 2h - Day 7
|
-3.5 msec
Standard Deviation 5.7
|
-1.5 msec
Standard Deviation 3.4
|
4.0 msec
Standard Deviation 4.3
|
-14.7 msec
Standard Deviation 14.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from pre-dose Day 7 at 4h
|
-9.0 msec
Standard Deviation 9.0
|
-1.0 msec
Standard Deviation 3.8
|
0.0 msec
Standard Deviation 1.6
|
-14.3 msec
Standard Deviation 15.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from pre-dose Day 7 BL at 6h - Day 7
|
-13.0 msec
Standard Deviation 4.8
|
-3.5 msec
Standard Deviation 8.2
|
-4.5 msec
Standard Deviation 2.5
|
-6.7 msec
Standard Deviation 5.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from pre-dose Day 7 at 8h - Day 7
|
-10.0 msec
Standard Deviation 5.9
|
0.0 msec
Standard Deviation 7.3
|
-5.0 msec
Standard Deviation 2.6
|
-11.3 msec
Standard Deviation 4.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from pre-dose Day 7 at 12h - Day 7
|
-24.0 msec
Standard Deviation 23.6
|
-1.5 msec
Standard Deviation 5.7
|
-4.5 msec
Standard Deviation 4.1
|
-4.0 msec
Standard Deviation 7.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from BL at pre-dose Day 2
|
-5.8 msec
Standard Deviation 6.1
|
-0.5 msec
Standard Deviation 1.9
|
2.0 msec
Standard Deviation 6.6
|
-6.5 msec
Standard Deviation 14.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from BL at pre-dose Day 3
|
6.3 msec
Standard Deviation 5.4
|
4.5 msec
Standard Deviation 2.5
|
0.0 msec
Standard Deviation 6.8
|
-6.8 msec
Standard Deviation 7.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from BL at pre-dose Day 4
|
6.3 msec
Standard Deviation 3.3
|
9.5 msec
Standard Deviation 1.0
|
7.5 msec
Standard Deviation 6.8
|
-3.8 msec
Standard Deviation 19.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from BL at pre-dose Day 5
|
-2.3 msec
Standard Deviation 7.4
|
4.0 msec
Standard Deviation 6.2
|
8.5 msec
Standard Deviation 10.1
|
-2.2 msec
Standard Deviation 16.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval)
Change from BL at pre-dose Day 6
|
-0.3 msec
Standard Deviation 9.5
|
3.0 msec
Standard Deviation 4.3
|
6.0 msec
Standard Deviation 3.5
|
5.2 msec
Standard Deviation 19.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-upThe baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Baseline (Pre-dose Day 1)
|
99.3 msec
Standard Deviation 6.9
|
92.5 msec
Standard Deviation 6.1
|
85.5 msec
Standard Deviation 8.3
|
98.5 msec
Standard Deviation 8.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL Day 7 BL at 6h - Day 7
|
0.5 msec
Standard Deviation 1.9
|
-2.5 msec
Standard Deviation 2.5
|
3.0 msec
Standard Deviation 2.0
|
0.7 msec
Standard Deviation 2.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL at 2h - Day 1
|
1.3 msec
Standard Deviation 1.0
|
2.0 msec
Standard Deviation 1.4
|
6.0 msec
Standard Deviation 2.9
|
-0.2 msec
Standard Deviation 1.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL at 24h - Day 1
|
0.3 msec
Standard Deviation 2.1
|
2.5 msec
Standard Deviation 2.4
|
3.5 msec
Standard Deviation 2.6
|
-0.8 msec
Standard Deviation 1.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Baseline (pre-dose Day 7)
|
99.5 msec
Standard Deviation 7.2
|
97.0 msec
Standard Deviation 5.3
|
87.5 msec
Standard Deviation 7.2
|
98.7 msec
Standard Deviation 8.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL Day 7 at 2h - Day 7
|
0.5 msec
Standard Deviation 1.9
|
1.0 msec
Standard Deviation 1.2
|
5.5 msec
Standard Deviation 1.9
|
0.7 msec
Standard Deviation 2.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL Day 7 at 4h
|
0.0 msec
Standard Deviation 2.8
|
-0.5 msec
Standard Deviation 1.0
|
2.5 msec
Standard Deviation 2.5
|
0.7 msec
Standard Deviation 3.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL Day 7 at 8h - Day 7
|
-3.5 msec
Standard Deviation 1.9
|
-0.5 msec
Standard Deviation 1.9
|
2.0 msec
Standard Deviation 1.6
|
0.7 msec
Standard Deviation 4.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL Day 7 at 12h - Day 7
|
-1.5 msec
Standard Deviation 3.0
|
-2.0 msec
Standard Deviation 1.6
|
2.0 msec
Standard Deviation 0.0
|
-2.0 msec
Standard Deviation 3.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL at pre-dose Day 2
|
0.3 msec
Standard Deviation 2.1
|
2.5 msec
Standard Deviation 2.4
|
3.5 msec
Standard Deviation 2.6
|
-0.8 msec
Standard Deviation 1.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL at pre-dose Day 3
|
0.3 msec
Standard Deviation 2.1
|
2.5 msec
Standard Deviation 1.3
|
2.0 msec
Standard Deviation 3.7
|
-0.8 msec
Standard Deviation 2.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL at pre-dose Day 4
|
-0.8 msec
Standard Deviation 1.5
|
5.0 msec
Standard Deviation 3.4
|
3.5 msec
Standard Deviation 1.7
|
-0.5 msec
Standard Deviation 2.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL at pre-dose Day 5
|
-0.8 msec
Standard Deviation 1.5
|
2.5 msec
Standard Deviation 0.6
|
2.5 msec
Standard Deviation 1.7
|
-0.5 msec
Standard Deviation 2.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL at pre-dose Day 6
|
-0.3 msec
Standard Deviation 1.3
|
2.0 msec
Standard Deviation 2.4
|
1.0 msec
Standard Deviation 2.2
|
-1.8 msec
Standard Deviation 2.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL at pre-dose Day 7
|
0.3 msec
Standard Deviation 0.5
|
4.5 msec
Standard Deviation 1.3
|
2.0 msec
Standard Deviation 1.4
|
0.2 msec
Standard Deviation 3.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL at FU
|
0.3 msec
Standard Deviation 2.6
|
0.5 msec
Standard Deviation 1.7
|
-2.5 msec
Standard Deviation 2.4
|
-1.8 msec
Standard Deviation 5.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval)
Change from BL Day 7 at 1h - Day 7
|
0.5 msec
Standard Deviation 3.0
|
0.0 msec
Standard Deviation 2.8
|
5.0 msec
Standard Deviation 2.0
|
-0.3 msec
Standard Deviation 0.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-upPopulation: Per protocol set
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=6 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at 2h - Day 1
|
-5.5 msec
Standard Deviation 10.5
|
-7.5 msec
Standard Deviation 16.0
|
-4.0 msec
Standard Deviation 3.7
|
4.2 msec
Standard Deviation 10.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from pre-dose Day 7 at 4h
|
-7.0 msec
Standard Deviation 1.2
|
-2.0 msec
Standard Deviation 7.1
|
-4.0 msec
Standard Deviation 11.9
|
10.7 msec
Standard Deviation 15.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Baseline (Pre-dose Day 1)
|
410.5 msec
Standard Deviation 41.8
|
391.5 msec
Standard Deviation 8.5
|
399.0 msec
Standard Deviation 11.2
|
410.2 msec
Standard Deviation 33.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at 24h - Day 1
|
-10.0 msec
Standard Deviation 11.9
|
1.0 msec
Standard Deviation 8.8
|
-14.5 msec
Standard Deviation 4.8
|
-4.2 msec
Standard Deviation 14.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Baseline (pre-dose Day 7)
|
393.0 msec
Standard Deviation 42.6
|
388.5 msec
Standard Deviation 20.6
|
402.0 msec
Standard Deviation 18.8
|
406.0 msec
Standard Deviation 22.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from pre-dose Day 7 at 1h - Day 7
|
5.0 msec
Standard Deviation 12.4
|
-1.0 msec
Standard Deviation 7.4
|
0.0 msec
Standard Deviation 9.1
|
1.0 msec
Standard Deviation 8.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from pre-dose Day 7 at 2h - Day 7
|
0.0 msec
Standard Deviation 6.5
|
-10.5 msec
Standard Deviation 15.4
|
-7.5 msec
Standard Deviation 10.0
|
-2.3 msec
Standard Deviation 14.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from pre-dose Day 7 BL at 6h - Day 7
|
-15.5 msec
Standard Deviation 14.2
|
-17.0 msec
Standard Deviation 15.2
|
-16.5 msec
Standard Deviation 10.6
|
-14.3 msec
Standard Deviation 26.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from pre-dose Day 7 at 8h - Day 7
|
-18.5 msec
Standard Deviation 13.7
|
-1.0 msec
Standard Deviation 12.7
|
-11.0 msec
Standard Deviation 11.9
|
-3.0 msec
Standard Deviation 17.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from pre-dose Day 7 at 12h - Day 7
|
-20.0 msec
Standard Deviation 14.1
|
-20.0 msec
Standard Deviation 6.3
|
-11.5 msec
Standard Deviation 9.6
|
-8.7 msec
Standard Deviation 19.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at pre-dose Day 2
|
-10.0 msec
Standard Deviation 11.9
|
1.0 msec
Standard Deviation 8.8
|
-14.5 msec
Standard Deviation 4.8
|
-4.2 msec
Standard Deviation 14.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at pre-dose Day 3
|
-10.5 msec
Standard Deviation 20.0
|
7.5 msec
Standard Deviation 6.6
|
-10.0 msec
Standard Deviation 9.6
|
-6.2 msec
Standard Deviation 12.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at pre-dose Day 4
|
-6.0 msec
Standard Deviation 26.1
|
-3.5 msec
Standard Deviation 13.4
|
6.0 msec
Standard Deviation 4.5
|
-0.2 msec
Standard Deviation 20.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at pre-dose Day 5
|
-9.0 msec
Standard Deviation 24.9
|
-13.0 msec
Standard Deviation 11.9
|
3.0 msec
Standard Deviation 9.4
|
1.2 msec
Standard Deviation 16.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at pre-dose Day 6
|
-16.0 msec
Standard Deviation 23.5
|
-0.5 msec
Standard Deviation 12.2
|
-4.5 msec
Standard Deviation 10.1
|
-3.8 msec
Standard Deviation 11.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at pre-dose Day 7
|
-17.5 msec
Standard Deviation 32.3
|
-3.0 msec
Standard Deviation 14.8
|
3.0 msec
Standard Deviation 9.4
|
-4.2 msec
Standard Deviation 16.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
MAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at FU
|
-22.0 msec
Standard Deviation 13.2
|
-10.5 msec
Standard Deviation 14.6
|
-23.0 msec
Standard Deviation 14.3
|
13.2 msec
Standard Deviation 23.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, Day 1, Day 7Population: Per protocol set
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Change from BLat 12h post dose
|
-1.8 msec
Standard Deviation 4.7
|
-3.7 msec
Standard Deviation 8.3
|
-4.0 msec
Standard Deviation 4.8
|
-1.8 msec
Standard Deviation 4.9
|
-6.5 msec
Standard Deviation 4.4
|
-9.5 msec
Standard Deviation 10.6
|
-4.3 msec
Standard Deviation 5.7
|
0.5 msec
Standard Deviation 7.7
|
-9.0 msec
Standard Deviation 12.7
|
-1.5 msec
Standard Deviation 4.7
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Change from BL at 24h post dose
|
-2.2 msec
Standard Deviation 3.3
|
-3.7 msec
Standard Deviation 8.5
|
-4.5 msec
Standard Deviation 8.4
|
-4.3 msec
Standard Deviation 2.6
|
-7.0 msec
Standard Deviation 3.5
|
-6.5 msec
Standard Deviation 3.0
|
-4.3 msec
Standard Deviation 4.9
|
-5.5 msec
Standard Deviation 8.9
|
0.0 msec
Standard Deviation 0.0
|
-2.0 msec
Standard Deviation 2.8
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Change from BL at FU
|
-5.5 msec
Standard Deviation 4.9
|
-1.3 msec
Standard Deviation 7.4
|
-5.0 msec
Standard Deviation 4.3
|
-7.3 msec
Standard Deviation 2.2
|
-11.0 msec
Standard Deviation 5.3
|
-3.0 msec
Standard Deviation 9.3
|
-9.8 msec
Standard Deviation 4.9
|
-7.0 msec
Standard Deviation 2.6
|
-16.0 msec
Standard Deviation 14.1
|
-3.5 msec
Standard Deviation 5.0
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Baseline (Pre-dose Day 1)
|
195.5 msec
Standard Deviation 28.9
|
165.0 msec
Standard Deviation 21.6
|
154.5 msec
Standard Deviation 39.2
|
159.8 msec
Standard Deviation 23.0
|
155.0 msec
Standard Deviation 24.4
|
176.5 msec
Standard Deviation 21.4
|
171.8 msec
Standard Deviation 15.9
|
176.0 msec
Standard Deviation 17.7
|
177.0 msec
Standard Deviation 26.9
|
147.5 msec
Standard Deviation 25.2
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Change from baseline at 1h
|
-1.2 msec
Standard Deviation 4.0
|
3.3 msec
Standard Deviation 7.4
|
-0.5 msec
Standard Deviation 1.9
|
-1.3 msec
Standard Deviation 5.7
|
-4.0 msec
Standard Deviation 3.7
|
4.0 msec
Standard Deviation 2.8
|
8.8 msec
Standard Deviation 3.0
|
20.5 msec
Standard Deviation 7.5
|
-9.0 msec
Standard Deviation 9.9
|
-3.5 msec
Standard Deviation 4.4
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Change from BL at 2h post dose
|
1.2 msec
Standard Deviation 3.9
|
-0.7 msec
Standard Deviation 3.7
|
-3.0 msec
Standard Deviation 3.7
|
1.3 msec
Standard Deviation 3.8
|
-3.0 msec
Standard Deviation 3.8
|
4.5 msec
Standard Deviation 5.7
|
8.3 msec
Standard Deviation 11.8
|
16.0 msec
Standard Deviation 5.9
|
-11.0 msec
Standard Deviation 9.9
|
-1.0 msec
Standard Deviation 2.6
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Change from BL at 4h post dose
|
-1.5 msec
Standard Deviation 8.8
|
-2.3 msec
Standard Deviation 0.8
|
-2.0 msec
Standard Deviation 2.6
|
4.8 msec
Standard Deviation 4.4
|
-3.5 msec
Standard Deviation 5.3
|
0.0 msec
Standard Deviation 4.0
|
3.3 msec
Standard Deviation 5.7
|
10.0 msec
Standard Deviation 6.3
|
-5.0 msec
Standard Deviation 7.1
|
-1.5 msec
Standard Deviation 3.0
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Change from BL at 6h post dose
|
-1.2 msec
Standard Deviation 3.6
|
-2.7 msec
Standard Deviation 3.3
|
-2.0 msec
Standard Deviation 2.6
|
0.8 msec
Standard Deviation 7.2
|
-7.5 msec
Standard Deviation 5.3
|
-5.5 msec
Standard Deviation 8.5
|
-3.3 msec
Standard Deviation 8.8
|
9.0 msec
Standard Deviation 6.0
|
-11.0 msec
Standard Deviation 12.7
|
-1.5 msec
Standard Deviation 1.9
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: PQ Interval
Change from BL at 8h post dose
|
-3.2 msec
Standard Deviation 3.6
|
1.0 msec
Standard Deviation 6.2
|
-6.5 msec
Standard Deviation 5.5
|
-1.3 msec
Standard Deviation 7.4
|
-8.0 msec
Standard Deviation 4.3
|
-8.0 msec
Standard Deviation 8.6
|
-5.3 msec
Standard Deviation 7.8
|
1.0 msec
Standard Deviation 10.4
|
-6.0 msec
Standard Deviation 2.8
|
-4.0 msec
Standard Deviation 3.7
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, Day 1, Day 7Population: Per protocol set
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Change from BL at 8h post dose
|
-2.0 msec
Standard Deviation 2.8
|
-1.0 msec
Standard Deviation 1.3
|
1.3 msec
Standard Deviation 3.3
|
-0.8 msec
Standard Deviation 2.1
|
-2.0 msec
Standard Deviation 1.6
|
2.5 msec
Standard Deviation 1.9
|
0.0 msec
Standard Deviation 6.7
|
13.0 msec
Standard Deviation 4.8
|
0.0 msec
Standard Deviation 0.0
|
-0.5 msec
Standard Deviation 1.9
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Change from BL at 12h post dose
|
-0.7 msec
Standard Deviation 3.6
|
-1.7 msec
Standard Deviation 1.0
|
0.3 msec
Standard Deviation 2.5
|
-0.3 msec
Standard Deviation 2.5
|
-1.5 msec
Standard Deviation 2.5
|
1.0 msec
Standard Deviation 2.6
|
2.5 msec
Standard Deviation 3.0
|
7.0 msec
Standard Deviation 2.0
|
0.0 msec
Standard Deviation 0.0
|
-2.5 msec
Standard Deviation 3.0
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Change from BL at 24h post dose
|
-2.7 msec
Standard Deviation 5.3
|
-1.7 msec
Standard Deviation 3.4
|
-1.3 msec
Standard Deviation 0.5
|
-2.3 msec
Standard Deviation 2.2
|
-1.5 msec
Standard Deviation 1.9
|
1.5 msec
Standard Deviation 4.4
|
0.0 msec
Standard Deviation 1.6
|
4.0 msec
Standard Deviation 0.0
|
-3.0 msec
Standard Deviation 4.2
|
-1.0 msec
Standard Deviation 2.0
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Baseline (Pre-dose Day 1)
|
103.0 msec
Standard Deviation 8.3
|
97.0 msec
Standard Deviation 9.6
|
99.3 msec
Standard Deviation 3.3
|
97.8 msec
Standard Deviation 7.6
|
106.5 msec
Standard Deviation 10.2
|
92.5 msec
Standard Deviation 13.9
|
104.5 msec
Standard Deviation 10.6
|
94.0 msec
Standard Deviation 8.8
|
95.0 msec
Standard Deviation 7.1
|
105.5 msec
Standard Deviation 8.3
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Change from baseline at 1h
|
-0.7 msec
Standard Deviation 2.0
|
1.0 msec
Standard Deviation 5.2
|
-1.3 msec
Standard Deviation 0.5
|
0.3 msec
Standard Deviation 2.2
|
0.0 msec
Standard Deviation 2.8
|
3.5 msec
Standard Deviation 3.4
|
1.5 msec
Standard Deviation 6.4
|
26.0 msec
Standard Deviation 6.9
|
1.0 msec
Standard Deviation 1.4
|
0.0 msec
Standard Deviation 2.8
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Change from BL at 2h post dose
|
-2.0 msec
Standard Deviation 3.0
|
0.7 msec
Standard Deviation 3.2
|
-1.3 msec
Standard Deviation 1.3
|
-0.3 msec
Standard Deviation 1.0
|
-2.5 msec
Standard Deviation 1.0
|
3.0 msec
Standard Deviation 2.6
|
2.5 msec
Standard Deviation 7.2
|
20.5 msec
Standard Deviation 7.7
|
0.0 msec
Standard Deviation 0.0
|
-2.0 msec
Standard Deviation 2.8
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Change from BL at 4h post dose
|
-1.0 msec
Standard Deviation 3.0
|
-0.7 msec
Standard Deviation 2.2
|
-1.3 msec
Standard Deviation 1.7
|
-0.8 msec
Standard Deviation 0.5
|
-2.0 msec
Standard Deviation 0.0
|
2.0 msec
Standard Deviation 2.8
|
2.5 msec
Standard Deviation 3.0
|
17.0 msec
Standard Deviation 6.0
|
0.0 msec
Standard Deviation 2.8
|
-3.5 msec
Standard Deviation 3.4
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Change from BL at 6h post dose
|
0.3 msec
Standard Deviation 3.8
|
0.3 msec
Standard Deviation 1.6
|
0.8 msec
Standard Deviation 2.6
|
-0.3 msec
Standard Deviation 2.8
|
-1.5 msec
Standard Deviation 1.0
|
3.5 msec
Standard Deviation 2.5
|
1.5 msec
Standard Deviation 2.5
|
14.5 msec
Standard Deviation 5.3
|
1.0 msec
Standard Deviation 1.4
|
-1.5 msec
Standard Deviation 3.4
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QRS Interval
Change from BL at FU
|
-1.3 msec
Standard Deviation 6.2
|
-0.7 msec
Standard Deviation 4.4
|
-1.3 msec
Standard Deviation 3.5
|
0.8 msec
Standard Deviation 6.4
|
-2.5 msec
Standard Deviation 4.1
|
0.0 msec
Standard Deviation 3.3
|
-3.0 msec
Standard Deviation 5.3
|
-0.5 msec
Standard Deviation 2.5
|
-1.0 msec
Standard Deviation 4.2
|
-1.5 msec
Standard Deviation 4.7
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, Day 1, Day 7Population: Per protocol set
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at FU
|
-12.0 msec
Standard Deviation 4.3
|
-18.3 msec
Standard Deviation 11.4
|
-13.8 msec
Standard Deviation 6.7
|
-12.5 msec
Standard Deviation 9.8
|
-9.0 msec
Standard Deviation 5.0
|
-12.0 msec
Standard Deviation 13.4
|
-8.3 msec
Standard Deviation 12.4
|
-7.8 msec
Standard Deviation 10.1
|
-2.0 msec
Standard Deviation 25.5
|
-1.0 msec
Standard Deviation 8.9
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Baseline (Pre-dose Day 1)
|
400.0 msec
Standard Deviation 18.6
|
415.0 msec
Standard Deviation 23.5
|
393.3 msec
Standard Deviation 15.4
|
416.0 msec
Standard Deviation 15.6
|
404.0 msec
Standard Deviation 11.4
|
409.0 msec
Standard Deviation 28.2
|
396.3 msec
Standard Deviation 15.9
|
398.3 msec
Standard Deviation 17.3
|
373.0 msec
Standard Deviation 7.1
|
396.0 msec
Standard Deviation 12.8
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at 2h post dose
|
3.0 msec
Standard Deviation 8.5
|
-7.3 msec
Standard Deviation 16.2
|
4.8 msec
Standard Deviation 21.4
|
0.5 msec
Standard Deviation 9.7
|
9.0 msec
Standard Deviation 10.9
|
-2.5 msec
Standard Deviation 6.6
|
3.3 msec
Standard Deviation 17.1
|
4.8 msec
Standard Deviation 21.9
|
-2.0 msec
Standard Deviation 5.7
|
16.0 msec
Standard Deviation 11.7
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at 4h post dose
|
9.3 msec
Standard Deviation 7.5
|
-3.7 msec
Standard Deviation 16.9
|
3.3 msec
Standard Deviation 9.0
|
6.0 msec
Standard Deviation 7.1
|
7.0 msec
Standard Deviation 12.9
|
-2.0 msec
Standard Deviation 11.4
|
-3.8 msec
Standard Deviation 16.7
|
1.8 msec
Standard Deviation 14.6
|
7.0 msec
Standard Deviation 4.2
|
-4.0 msec
Standard Deviation 8.5
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at 8h post dose
|
-8.7 msec
Standard Deviation 4.4
|
-24.0 msec
Standard Deviation 9.9
|
-6.8 msec
Standard Deviation 9.1
|
-18.5 msec
Standard Deviation 4.0
|
-4.0 msec
Standard Deviation 16.6
|
-16.0 msec
Standard Deviation 9.8
|
-14.8 msec
Standard Deviation 9.3
|
-5.3 msec
Standard Deviation 7.1
|
-17.0 msec
Standard Deviation 15.6
|
-9.0 msec
Standard Deviation 9.3
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at 12h post dose
|
-8.7 msec
Standard Deviation 3.3
|
-24.3 msec
Standard Deviation 16.3
|
-2.8 msec
Standard Deviation 9.0
|
-15.5 msec
Standard Deviation 11.2
|
-6.5 msec
Standard Deviation 13.0
|
-22.5 msec
Standard Deviation 6.8
|
-12.3 msec
Standard Deviation 7.5
|
-13.3 msec
Standard Deviation 15.9
|
-18.0 msec
Standard Deviation 17.0
|
-10.0 msec
Standard Deviation 15.5
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from baseline at 1h
|
9.7 msec
Standard Deviation 12.7
|
-4.3 msec
Standard Deviation 13.6
|
2.3 msec
Standard Deviation 6.4
|
-8.5 msec
Standard Deviation 9.5
|
10.5 msec
Standard Deviation 5.3
|
-3.0 msec
Standard Deviation 7.4
|
-5.8 msec
Standard Deviation 17.6
|
8.8 msec
Standard Deviation 22.7
|
-11.0 msec
Standard Deviation 1.4
|
-15.5 msec
Standard Deviation 14.3
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at 6h post dose
|
-6.7 msec
Standard Deviation 8.8
|
-16.0 msec
Standard Deviation 14.8
|
-9.8 msec
Standard Deviation 8.5
|
-19.5 msec
Standard Deviation 7.4
|
-3.5 msec
Standard Deviation 13.2
|
-11.0 msec
Standard Deviation 6.2
|
-19.3 msec
Standard Deviation 9.2
|
-4.8 msec
Standard Deviation 16.3
|
-14.0 msec
Standard Deviation 5.7
|
-13.0 msec
Standard Deviation 8.4
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QT Interval
Change from BL at 24h post dose
|
-6.7 msec
Standard Deviation 6.1
|
-23.0 msec
Standard Deviation 13.5
|
-11.8 msec
Standard Deviation 3.0
|
-15.5 msec
Standard Deviation 16.5
|
-4.5 msec
Standard Deviation 8.2
|
-17.0 msec
Standard Deviation 14.7
|
-10.3 msec
Standard Deviation 13.3
|
2.3 msec
Standard Deviation 4.9
|
-3.0 msec
Standard Deviation 18.4
|
-7.0 msec
Standard Deviation 3.8
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose, Day1, Day 7Population: Per protocol set
The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline.
Outcome measures
| Measure |
Group I Placebo
n=6 Participants
Placebo - single dose
|
Group II Placebo
n=6 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 Participants
2000mg KH176 - single dose
|
Group I Placebo + Food
n=4 Participants
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=2 Participants
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Change from BL at 1h
|
1.7 msec
Standard Deviation 7.7
|
-0.7 msec
Standard Deviation 10.1
|
-1.0 msec
Standard Deviation 2.8
|
-0.3 msec
Standard Deviation 6.7
|
-3.5 msec
Standard Deviation 5.0
|
1.8 msec
Standard Deviation 7.3
|
3.0 msec
Standard Deviation 8.6
|
39.0 msec
Standard Deviation 19.0
|
12.5 msec
Standard Deviation 29.0
|
16.0 msec
Standard Deviation 7.9
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Change from BL at 4h post dose
|
5.5 msec
Standard Deviation 15.2
|
-1.5 msec
Standard Deviation 17.1
|
-7.3 msec
Standard Deviation 3.3
|
-8.3 msec
Standard Deviation 11.9
|
-1.5 msec
Standard Deviation 7.0
|
6.0 msec
Standard Deviation 17.8
|
6.5 msec
Standard Deviation 6.2
|
38.5 msec
Standard Deviation 10.7
|
9.0 msec
Standard Deviation 28.3
|
1.8 msec
Standard Deviation 8.2
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Change from BL at 6h post dose
|
12.7 msec
Standard Deviation 4.8
|
3.7 msec
Standard Deviation 8.4
|
11.5 msec
Standard Deviation 5.8
|
4.0 msec
Standard Deviation 13.1
|
0.0 msec
Standard Deviation 14.9
|
14.0 msec
Standard Deviation 11.0
|
17.8 msec
Standard Deviation 1.0
|
41.8 msec
Standard Deviation 13.8
|
20.0 msec
Standard Deviation 15.6
|
15.5 msec
Standard Deviation 6.6
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Change from BL at 8h post dose
|
3.0 msec
Standard Deviation 12.3
|
1.2 msec
Standard Deviation 9.3
|
-4.8 msec
Standard Deviation 7.8
|
6.8 msec
Standard Deviation 14.2
|
8.5 msec
Standard Deviation 18.7
|
5.5 msec
Standard Deviation 12.1
|
8.0 msec
Standard Deviation 7.4
|
37.5 msec
Standard Deviation 19.3
|
5.0 msec
Standard Deviation 12.7
|
5.0 msec
Standard Deviation 6.5
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Change from BL at 24h post dose
|
11.7 msec
Standard Deviation 19.3
|
0.0 msec
Standard Deviation 8.6
|
0.0 msec
Standard Deviation 11.3
|
0.8 msec
Standard Deviation 15.1
|
3.0 msec
Standard Deviation 7.1
|
1.5 msec
Standard Deviation 6.5
|
5.3 msec
Standard Deviation 9.0
|
15.8 msec
Standard Deviation 4.9
|
-0.5 msec
Standard Deviation 21.9
|
-2.5 msec
Standard Deviation 5.7
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Baseline (Pre-dose Day 1)
|
379.3 msec
Standard Deviation 21.0
|
385.5 msec
Standard Deviation 9.8
|
382.0 msec
Standard Deviation 21.4
|
390.5 msec
Standard Deviation 8.9
|
383.8 msec
Standard Deviation 24.8
|
386.3 msec
Standard Deviation 8.0
|
382.0 msec
Standard Deviation 10.9
|
378.5 msec
Standard Deviation 19.1
|
367.5 msec
Standard Deviation 24.7
|
382.3 msec
Standard Deviation 22.0
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Change from BL at 2h post dose
|
-0.5 msec
Standard Deviation 12.8
|
-2.8 msec
Standard Deviation 9.3
|
-4.0 msec
Standard Deviation 18.2
|
-6.5 msec
Standard Deviation 7.9
|
-10.8 msec
Standard Deviation 9.6
|
3.0 msec
Standard Deviation 8.4
|
9.8 msec
Standard Deviation 8.3
|
41.3 msec
Standard Deviation 21.7
|
4.5 msec
Standard Deviation 25.3
|
10.3 msec
Standard Deviation 4.0
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Change from BL at 12h post dose
|
7.0 msec
Standard Deviation 8.3
|
3.8 msec
Standard Deviation 8.9
|
-1.0 msec
Standard Deviation 2.2
|
-2.8 msec
Standard Deviation 14.0
|
2.8 msec
Standard Deviation 13.0
|
11.5 msec
Standard Deviation 13.1
|
17.8 msec
Standard Deviation 5.2
|
36.0 msec
Standard Deviation 9.4
|
17.5 msec
Standard Deviation 2.1
|
9.5 msec
Standard Deviation 10.3
|
—
|
—
|
—
|
—
|
|
SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval
Change from BL at FU
|
5.3 msec
Standard Deviation 17.6
|
13.0 msec
Standard Deviation 15.4
|
4.8 msec
Standard Deviation 18.8
|
10.8 msec
Standard Deviation 15.9
|
8.3 msec
Standard Deviation 19.8
|
13.3 msec
Standard Deviation 12.7
|
-3.5 msec
Standard Deviation 6.5
|
9.0 msec
Standard Deviation 14.4
|
9.0 msec
Standard Deviation 28.3
|
9.8 msec
Standard Deviation 18.5
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD
|
0 hours
Geometric Coefficient of Variation 0
|
10.3 hours
Geometric Coefficient of Variation 14.6
|
9.10 hours
Geometric Coefficient of Variation 15.2
|
9.64 hours
Geometric Coefficient of Variation 4.29
|
9.80 hours
Geometric Coefficient of Variation 19.1
|
11.5 hours
Geometric Coefficient of Variation 4.73
|
9.09 hours
Geometric Coefficient of Variation 3.83
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Terminal Elimination Half-life (T1/2) of KH183: SAD
|
16.6 hours
Geometric Coefficient of Variation 5.86
|
17.8 hours
Geometric Coefficient of Variation 19.0
|
15.4 hours
Geometric Coefficient of Variation 8.44
|
14.3 hours
Geometric Coefficient of Variation 18.9
|
17.2 hours
Geometric Coefficient of Variation 18.5
|
18.9 hours
Geometric Coefficient of Variation 18.7
|
14.9 hours
Geometric Coefficient of Variation 7.86
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Concentration (Cmax) of KH176: SAD Group
|
12.9 ng/mL
Geometric Coefficient of Variation 21.3
|
56.2 ng/mL
Geometric Coefficient of Variation 21.0
|
167 ng/mL
Geometric Coefficient of Variation 27.2
|
766 ng/mL
Geometric Coefficient of Variation 53.9
|
2170 ng/mL
Geometric Coefficient of Variation 27.9
|
5990 ng/mL
Geometric Coefficient of Variation 20.9
|
165 ng/mL
Geometric Coefficient of Variation 7.40
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD
|
14.2 ng/mL
Geometric Coefficient of Variation 49.5
|
49.4 ng/mL
Geometric Coefficient of Variation 9.00
|
168 ng/mL
Geometric Coefficient of Variation 29.6
|
497 ng/mL
Geometric Coefficient of Variation 17.6
|
1100 ng/mL
Geometric Coefficient of Variation 9.58
|
1780 ng/mL
Geometric Coefficient of Variation 26.3
|
117 ng/mL
Geometric Coefficient of Variation 20.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hoursPopulation: Per protocol set
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group
Day 1
|
99.4 ng/mL
Geometric Coefficient of Variation 20.9
|
251 ng/mL
Geometric Coefficient of Variation 18.0
|
550 ng/mL
Geometric Coefficient of Variation 14.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group
Day 7
|
152 ng/mL
Geometric Coefficient of Variation 37.5
|
250 ng/mL
Geometric Coefficient of Variation 10.6
|
450 ng/mL
Geometric Coefficient of Variation 28.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hoursPopulation: Per protocol set
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Concentration (Cmax) of KH176: MAD
Day 1
|
184 ng/mL
Geometric Coefficient of Variation 57.0
|
313 ng/mL
Geometric Coefficient of Variation 20.0
|
1330 ng/mL
Geometric Coefficient of Variation 27.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Maximum Concentration (Cmax) of KH176: MAD
Day 7
|
353 ng/mL
Geometric Coefficient of Variation 19.1
|
748 ng/mL
Geometric Coefficient of Variation 29.3
|
2100 ng/mL
Geometric Coefficient of Variation 27.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD
|
1.03 hours
Geometric Coefficient of Variation 55.5
|
1.03 hours
Geometric Coefficient of Variation 55.5
|
0.931 hours
Geometric Coefficient of Variation 83.4
|
1.10 hours
Geometric Coefficient of Variation 85.6
|
1.36 hours
Geometric Coefficient of Variation 20.5
|
0.931 hours
Geometric Coefficient of Variation 102
|
2.45 hours
Geometric Coefficient of Variation 23.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD
|
1.32 ng/mL
Geometric Coefficient of Variation 34.8
|
1.46 ng/mL
Geometric Coefficient of Variation 29.1
|
1.32 ng/mL
Geometric Coefficient of Variation 34.8
|
1.31 ng/mL
Geometric Coefficient of Variation 34.7
|
1.61 ng/mL
Geometric Coefficient of Variation 14.5
|
1.57 ng/mL
Geometric Coefficient of Variation 33.7
|
2.45 ng/mL
Geometric Coefficient of Variation 23.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hoursPopulation: Per protocol set
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group
Day 1
|
1.57 hours
Geometric Coefficient of Variation 173
|
1.73 hours
Geometric Coefficient of Variation 16.7
|
0.866 hours
Geometric Coefficient of Variation 70.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group
Day 7
|
0.931 hours
Geometric Coefficient of Variation 48.1
|
1.86 hours
Geometric Coefficient of Variation 14.5
|
1.36 hours
Geometric Coefficient of Variation 85.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hoursPopulation: Per protocol set
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group
Day 1
|
2.06 hours
Geometric Coefficient of Variation 116
|
1.57 hours
Geometric Coefficient of Variation 33.7
|
1.22 hours
Geometric Coefficient of Variation 23.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group
Day 7
|
1.19 hours
Geometric Coefficient of Variation 36.6
|
1.46 hours
Geometric Coefficient of Variation 29.1
|
1.61 hours
Geometric Coefficient of Variation 48.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hoursPopulation: Per protocol set
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group
|
2.52 ratio
Geometric Coefficient of Variation 31.2
|
2.65 ratio
Geometric Coefficient of Variation 2.5
|
2.17 ratio
Geometric Coefficient of Variation 14.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hoursPopulation: Per protocol set. The placebo subjects were excluded from the PK analysis per-protocol set.
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group
|
1.86 ratio
Geometric Coefficient of Variation 46.7
|
1.32 ratio
Geometric Coefficient of Variation 13.1
|
1.19 ratio
Geometric Coefficient of Variation 24.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group
|
151 h*ng/mL
Geometric Coefficient of Variation 26.7
|
547 h*ng/mL
Geometric Coefficient of Variation 12.4
|
1810 h*ng/mL
Geometric Coefficient of Variation 37.4
|
4830 h*ng/mL
Geometric Coefficient of Variation 11.8
|
11700 h*ng/mL
Geometric Coefficient of Variation 20.2
|
23900 h*ng/mL
Geometric Coefficient of Variation 22.2
|
1590 h*ng/mL
Geometric Coefficient of Variation 26.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group
|
75 h*ng/mL
Geometric Coefficient of Variation 14.8
|
389 h*ng/mL
Geometric Coefficient of Variation 8.16
|
1310 h*ng/mL
Geometric Coefficient of Variation 16.7
|
6320 h*ng/mL
Geometric Coefficient of Variation 20.2
|
21000 h*ng/mL
Geometric Coefficient of Variation 27.5
|
61200 h*ng/mL
Geometric Coefficient of Variation 9.07
|
1650 h*ng/mL
Geometric Coefficient of Variation 1.67
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hoursPopulation: Per protocol set
Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group:
Day 1
|
1090 h*ng/mL
Geometric Coefficient of Variation 49.3
|
2250 h*ng/mL
Geometric Coefficient of Variation 26.1
|
6890 h*ng/mL
Geometric Coefficient of Variation 19.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group:
Day 7
|
2760 h*ng/mL
Geometric Coefficient of Variation 22.6
|
5960 h*ng/mL
Geometric Coefficient of Variation 26.8
|
14900 h*ng/mL
Geometric Coefficient of Variation 28.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hoursPopulation: Per protocol set. The placebo subjects were excluded from the PharmaocoKinetics (PK) analysis per-protocol set.
Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group
Day 1
|
702 h*ng/mL
Geometric Coefficient of Variation 29.2
|
1680 h*ng/mL
Geometric Coefficient of Variation 21.0
|
3600 h*ng/mL
Geometric Coefficient of Variation 11.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group
Day 7
|
1310 h*ng/mL
Geometric Coefficient of Variation 29.5
|
2220 h*ng/mL
Geometric Coefficient of Variation 12.7
|
4270 h*ng/mL
Geometric Coefficient of Variation 30.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD
|
234 h*ng/mL
Geometric Coefficient of Variation 26.7
|
881 h*ng/mL
Geometric Coefficient of Variation 19.6
|
2690 h*ng/mL
Geometric Coefficient of Variation 38.4
|
6690 h*ng/mL
Geometric Coefficient of Variation 11.0
|
18700 h*ng/mL
Geometric Coefficient of Variation 26.7
|
41300 h*ng/mL
Geometric Coefficient of Variation 10.5
|
2410 h*ng/mL
Geometric Coefficient of Variation 29.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dosePopulation: Per protocol set
Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 Participants
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD
|
0 h*ng/mL
Geometric Coefficient of Variation 0
|
474 h*ng/mL
Geometric Coefficient of Variation 8.39
|
1540 h*ng/mL
Geometric Coefficient of Variation 13.1
|
7500 h*ng/mL
Geometric Coefficient of Variation 19.1
|
25800 h*ng/mL
Geometric Coefficient of Variation 33.9
|
79100 h*ng/mL
Geometric Coefficient of Variation 8.82
|
1970 h*ng/mL
Geometric Coefficient of Variation 1.04
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: Per protocol set
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=8 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
KH176: Percentage of Administered Dose Excreted in Urine: SAD
|
9.71 percentage of dose excreted
Geometric Coefficient of Variation 37.4
|
10.5 percentage of dose excreted
Geometric Coefficient of Variation 45.6
|
10.4 percentage of dose excreted
Geometric Coefficient of Variation 29.5
|
9.53 percentage of dose excreted
Geometric Coefficient of Variation 65.2
|
10.9 percentage of dose excreted
Geometric Coefficient of Variation 41.6
|
12.4 percentage of dose excreted
Geometric Coefficient of Variation 20.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: Per protocol set
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=8 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
KH183: Percentage of Administered Dose Excreted in Urine: SAD
|
4.56 percentage of dose excreted
Geometric Coefficient of Variation 53.0
|
6.42 percentage of dose excreted
Geometric Coefficient of Variation 14.5
|
5.18 percentage of dose excreted
Geometric Coefficient of Variation 28.8
|
3.81 percentage of dose excreted
Geometric Coefficient of Variation 82.9
|
3.86 percentage of dose excreted
Geometric Coefficient of Variation 31.0
|
3.33 percentage of dose excreted
Geometric Coefficient of Variation 32.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: Per protocol set
Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=8 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 Participants
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 Participants
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 Participants
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD
|
14.4 percentage of dose excreted
Geometric Coefficient of Variation 40.0
|
17.2 percentage of dose excreted
Geometric Coefficient of Variation 28.6
|
15.8 percentage of dose excreted
Geometric Coefficient of Variation 24.5
|
13.4 percentage of dose excreted
Geometric Coefficient of Variation 69.9
|
14.8 percentage of dose excreted
Geometric Coefficient of Variation 38.4
|
15.9 percentage of dose excreted
Geometric Coefficient of Variation 16.4
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 7 post dosePopulation: Per protocol set. The placebo subjects were excluded from the Pharmacokinetics (PK) analysis per-protocol set.
Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
KH176: Percentage of Administered Dose Excreted in Urine: MAD
|
14.9 percentage of dose excreted
Geometric Coefficient of Variation 77.8
|
13.4 percentage of dose excreted
Geometric Coefficient of Variation 36.4
|
14.0 percentage of dose excreted
Geometric Coefficient of Variation 14.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Post dose Day 7Population: Per protocol set. The placebo subjects were excluded from the Pharmacokinetics (PK) analysis per-protocol set.
Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
KH183: Percentage of Administered Dose Excreted in Urine: MAD
|
5.30 percentage of dose excreted
Geometric Coefficient of Variation 120.2
|
3.79 percentage of dose excreted
Geometric Coefficient of Variation 39.2
|
4.85 percentage of dose excreted
Geometric Coefficient of Variation 43.8
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 7 Post dosePopulation: Per protocol set. The placebo subjects were excluded from the Pharmacokinetics (PK) analysis per-protocol set.
Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.
Outcome measures
| Measure |
Group I Placebo
n=4 Participants
Placebo - single dose
|
Group II Placebo
n=4 Participants
Placebo - single dose
|
SAD Group I 10mg
n=4 Participants
10mg KH176 - single dose
|
SAD Group II 30mg
30mg KH176 - single dose
|
SAD Group I 100mg
100mg KH176 - single dose
|
SAD Group II 300mg
300mg KH176 - single dose
|
SAD Group I 800mg
800mg KH176 - single dose
|
SAD Group II 2000mg
2000mg KH176 - single dose
|
Group I Placebo + Food
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
400mg BID/Day (over 7 days)
|
Placebo
MAD group: Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD
|
20.7 percentage of dose excreted
Geometric Coefficient of Variation 79.3
|
17.4 percentage of dose excreted
Geometric Coefficient of Variation 33.3
|
19.0 percentage of dose excreted
Geometric Coefficient of Variation 17.9
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Group I Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Group II Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
SAD Group I 10mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
SAD Group II 30mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
SAD Group I 100mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
SAD Group II 300mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
SAD Group I 800mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
SAD Group II 2000mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Group I Placebo + Food
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Group I 100mg + Food
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
MAD Group III 200mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
MAD Group IV 400mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
MAD Group V 800mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group I Placebo
n=6 participants at risk
Placebo - single dose
|
Group II Placebo
n=6 participants at risk
Placebo - single dose
|
SAD Group I 10mg
n=4 participants at risk
10mg KH176 - single dose
|
SAD Group II 30mg
n=4 participants at risk
30mg KH176 - single dose
|
SAD Group I 100mg
n=4 participants at risk
100mg KH176 - single dose
|
SAD Group II 300mg
n=4 participants at risk
300mg KH176 - single dose
|
SAD Group I 800mg
n=4 participants at risk
800mg KH176 - single dose
|
SAD Group II 2000mg
n=4 participants at risk
2000mg KH176 - single dose
|
Group I Placebo + Food
n=2 participants at risk
Placebo + high calorie/high fat breakfast
|
Group I 100mg + Food
n=4 participants at risk
100mg KH176 + high calorie/high fat breakfast
|
MAD Group III 200mg
n=4 participants at risk
100mg BID/Day (over 7 days)
|
MAD Group IV 400mg
n=4 participants at risk
200mg BID/Day (over 7 days)
|
MAD Group V 800mg
n=4 participants at risk
400mg BID/Day (over 7 days)
|
Placebo
n=6 participants at risk
Placebo
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Psychiatric disorders
Bradyphrenia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Psychiatric disorders
Depersonalisation
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Psychiatric disorders
Hallucination, visual
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Nervous system disorders
Dizziness
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
75.0%
3/4 • Number of events 3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
75.0%
3/4 • Number of events 5
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
16.7%
1/6 • Number of events 4
|
|
Psychiatric disorders
Dysgeusia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
75.0%
3/4 • Number of events 3
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
25.0%
1/4 • Number of events 1
|
25.0%
1/4 • Number of events 3
|
50.0%
3/6 • Number of events 5
|
|
Nervous system disorders
Presyncope
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Cardiac disorders
Brundle branch block right
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal discomfort
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
|
Gastrointestinal disorders
Odynophagia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Paraesthesia oral
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
75.0%
3/4 • Number of events 3
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
50.0%
2/4 • Number of events 3
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
General disorders
Catheter site pain
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
General disorders
Chills
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
General disorders
Fatigue
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
General disorders
Influenza like illness
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
General disorders
Malaise
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 2
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Investigations
Blood pressure diastolic increased
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Investigations
Blood pressure systolic increased
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
75.0%
3/4 • Number of events 3
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Investigations
Eosinophil count increased
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
50.0%
1/2 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
25.0%
1/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Psychiatric disorders
Nightmare
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Head discomfort
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 2
|
0.00%
0/4
|
16.7%
1/6 • Number of events 2
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
25.0%
1/4 • Number of events 4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Eye disorders
Eye irritation
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
25.0%
1/4 • Number of events 2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Eye disorders
Vision blurred
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
50.0%
2/4 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
|
Renal and urinary disorders
Polyuria
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Feeling cold
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
General disorders
Feeling hot
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Investigations
Blood creatinine phosphokinase increased
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Investigations
Lipase increased
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/2
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place