Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of KQ-791 in Diabetes Mellitus (NCT NCT02445911)
NCT ID: NCT02445911
Last Updated: 2019-11-26
Results Overview
Data table is change from baseline in Fasting Blood Glucose. Statistical Analysis includes results for difference in Change from baseline in Fasting Blood Glucose Between KQ-791 and Placebo.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
81 participants
Primary outcome timeframe
Baseline to Day 29
Results posted on
2019-11-26
Participant Flow
Participant milestones
| Measure |
KQ-791 Dose 1
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
21
|
20
|
|
Overall Study
COMPLETED
|
20
|
20
|
21
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of KQ-791 in Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
Total
n=81 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
67 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
42 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
39 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
17 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
69 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
69 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
20 participants
n=7 Participants
|
21 participants
n=5 Participants
|
20 participants
n=4 Participants
|
81 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline to Day 29Population: Pharmacodynamic (PD) population incudes all 81 participants
Data table is change from baseline in Fasting Blood Glucose. Statistical Analysis includes results for difference in Change from baseline in Fasting Blood Glucose Between KQ-791 and Placebo.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo
|
-3.28 mg/dL milligrams per deciliters
Standard Deviation 22.99
|
-3.93 mg/dL milligrams per deciliters
Standard Deviation 30.63
|
0.67 mg/dL milligrams per deciliters
Standard Deviation 30.82
|
3.17 mg/dL milligrams per deciliters
Standard Deviation 23.17
|
PRIMARY outcome
Timeframe: Baseline to Day 29Population: PD population includes all 81 participants
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Number of Participants With One or More Treatment-Emergent Adverse Events
|
12 participants
|
12 participants
|
11 participants
|
14 participants
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: PD population includes all 81 participants
QUICKI = 1/(log FPG + log FPI) where FPG = fasting plasma glucose (mg/dL); FPI = fasting plasma insulin (estimated based on fasting serum insulin; (μIU/mL)). Lower numbers reflect greater insulin resistance.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI)
|
.0043 units on a scale
Standard Deviation .012
|
.003 units on a scale
Standard Deviation .013
|
.005 units on a scale
Standard Deviation .0125
|
-.0012 units on a scale
Standard Deviation .0116
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: Includes all subjects who receive at least one dose of study drug and have evaluable ISI data.
Insulin sensitivity index (ISI) composite using Matsuda's whole body insulin sensitivity, ISI \[composite\] = 10000/√\[(FPG x FPI)x(Mean Glucose 0-120min in MMTT x Mean Insulin 0-120 min in MMTT)\] where MMTT is a mixed meal tolerance test, Hour 0=just prior dosing. Lower values indicate greater insulin resistance.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=19 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Change From Baseline in the Insulin Sensitivity Index (ISI)
|
.0043 units on a scale
Standard Deviation 0.7345
|
-.0585 units on a scale
Standard Deviation 0.586
|
0.145 units on a scale
Standard Deviation 0.697
|
-0.112 units on a scale
Standard Deviation 0.669
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: PD population includes all 81 participants
Evaluated as beta index = (Insulin Area Under the Effect Curve (AUEC) in MMTT/Glucose AUEC in MMTT)
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Change From Baseline in Beta Cell Function
|
0.00098 (hr*μIU/mL(hr*mg/dL))
Standard Deviation 0.0866
|
0.012 (hr*μIU/mL(hr*mg/dL))
Standard Deviation 0.0585
|
0.0535 (hr*μIU/mL(hr*mg/dL))
Standard Deviation 0.1099
|
0.0027 (hr*μIU/mL(hr*mg/dL))
Standard Deviation 0.0491
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: Includes all subjects who receive at least one dose of study drug and have evaluable data for disposition index.
Disposition Index evaluated as beta index x ISI \[composite\]. Lower values of the disposition index suggests loss of function of beta cells.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=19 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Change From Baseline in Disposition Index
|
0.022 Index
Standard Deviation 0.128
|
0.023 Index
Standard Deviation 0.147
|
0.084 Index
Standard Deviation 0.185
|
0.008 Index
Standard Deviation 0.085
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: PD population includes all 81 participants
Hepatic Insulin Resistance Index will be evaluated as Glucose AUEC from zero to 30 minutes (AUEC0-30min) in MMTT x Insulin AUEC0-30 min in MMTT
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Change From Baseline in the Hepatic Insulin Resistance Index
|
99.51 (hr*mg/dL)*(hr*μUI/mL)
Standard Deviation 495.81
|
255.53 (hr*mg/dL)*(hr*μUI/mL)
Standard Deviation 484.27
|
93.17 (hr*mg/dL)*(hr*μUI/mL)
Standard Deviation 462.25
|
56.90 (hr*mg/dL)*(hr*μUI/mL)
Standard Deviation 482.72
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: PD population includes all 81 participants
The 7-points measured were just prior to each meal and 90 minutes after the start of the meal and approximately bedtime.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Change From Baseline in 7-point Average Blood Glucose
|
-5.04 mg/dL
Standard Deviation 20.76
|
0.35 mg/dL
Standard Deviation 35.74
|
-2.61 mg/dL
Standard Deviation 38.66
|
4.44 mg/dL
Standard Deviation 27.91
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: PD population includes all 81 participants
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Change From Baseline in Postprandial Glucose
|
-72.23 hr*mg/dL
Standard Deviation 281.62
|
-0.086 hr*mg/dL
Standard Deviation 484.712
|
-35.60 hr*mg/dL
Standard Deviation 524.57
|
58.61 hr*mg/dL
Standard Deviation 381.88
|
SECONDARY outcome
Timeframe: Baseline to Day 29Population: Includes all subjects who receive at least one dose of study drug and have evaluable HbA1c data.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=20 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=18 Participants
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Change From Baseline in HbA1c
|
-0.185 Percentage of glycosylated hemoglobin
Standard Deviation 0.3265
|
0.025 Percentage of glycosylated hemoglobin
Standard Deviation 0.4303
|
-0.315 Percentage of glycosylated hemoglobin
Standard Deviation 0.5174
|
-0.0333 Percentage of glycosylated hemoglobin
Standard Deviation 0.3343
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dosePopulation: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AUC0-24.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hours Post-Dose (AUC0-24)
|
14372.2 ng*hr/mL
Standard Deviation 2882.69
|
29011.2 ng*hr/mL
Standard Deviation 6030.57
|
140990.4 ng*hr/mL
Standard Deviation 47460.96
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dosePopulation: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Cmax.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
|
747.56 ng/mL
Standard Deviation 163.768
|
1484.74 ng/mL
Standard Deviation 341.712
|
7204.70 ng/mL
Standard Deviation 2517.201
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dosePopulation: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Tmax.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Time of the Maximum Measured Plasma Concentration (Tmax)
|
4.60 hours
Standard Deviation 3.251
|
5.05 hours
Standard Deviation 3.395
|
9.42 hours
Standard Deviation 8.663
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AUCtau.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve (AUCtau)
|
76863.5 ng*hr/mL
Standard Deviation 34469.47
|
25754.9 ng*hr/mL
Standard Deviation 13130.00
|
150681.0 ng*hr/mL
Standard Deviation 55372.30
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Cmax\_ss.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration at Steady-state (Cmax_ss)
|
657.82 ng/mL
Standard Deviation 238.542
|
1164.65 ng/mL
Standard Deviation 568.489
|
7221.37 ng/mL
Standard Deviation 2672.180
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Tmax\_ss.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Time of the Maximum Measured Plasma Concentration at Steady-state (Tmax_ss)
|
5.10 hours
Standard Deviation 5.00
|
5.43 hours
Standard Deviation 5.69
|
3.83 hours
Standard Deviation 3.40
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute t1/2.
Outcome measures
| Measure |
KQ-791 Dose 1
n=20 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Apparent Terminal Elimination Half-life (t1/2)
|
201.095 hours
Standard Deviation 79.378
|
184.386 hours
Standard Deviation 36.385
|
178.018 hours
Standard Deviation 28.389
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29Population: Includes all randomized subjects who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AI.
Based on AUC (RacAUC), where RacAUC is the ratio of AUC during a dosing interval following the last dose over the loading dose (first dose)
Outcome measures
| Measure |
KQ-791 Dose 1
n=19 Participants
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 Participants
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 Participants
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Accumulation Index (AI)
|
1.97 1/h
Standard Deviation 0.537
|
9.37 1/h
Standard Deviation 4.934
|
12.01 1/h
Standard Deviation 6.507
|
—
|
Adverse Events
KQ-791 Dose 1
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
KQ-791 Dose 2
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
KQ-791 Dose 3
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
KQ-791 Dose 1
n=20 participants at risk
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 participants at risk
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 participants at risk
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 participants at risk
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/21
|
5.0%
1/20 • Number of events 1
|
Other adverse events
| Measure |
KQ-791 Dose 1
n=20 participants at risk
Single loading dose of 100 mg on day 1, followed by single 50 mg doses on days 8, 15, 22, 29
KQ-791: Capsules administered orally
|
KQ-791 Dose 2
n=20 participants at risk
Single loading dose of 250 mg on day 1, followed by a daily dose of 25 mg for 28 days
KQ-791: Capsules administered orally
|
KQ-791 Dose 3
n=21 participants at risk
Single loading dose of 1500 mg on day 1, followed by a daily dose of 150 mg for 28 days
KQ-791: Capsules administered orally
|
Placebo
n=20 participants at risk
Multiple ascending doses matching KQ-791 dose
Placebo: Capsules administered orally
|
|---|---|---|---|---|
|
Eye disorders
Conjunctival irritation
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Eye disorders
Dry eye
|
5.0%
1/20
|
0.00%
0/20
|
9.5%
2/21
|
0.00%
0/20
|
|
Eye disorders
Ocular discomfort
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Gastrointestinal disorders
Abdominal discomfort
|
10.0%
2/20
|
25.0%
5/20
|
19.0%
4/21
|
0.00%
0/20
|
|
Gastrointestinal disorders
Abdominal pain
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Gastrointestinal disorders
Constipation
|
5.0%
1/20
|
10.0%
2/20
|
9.5%
2/21
|
10.0%
2/20
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
4/20
|
15.0%
3/20
|
28.6%
6/21
|
30.0%
6/20
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/21
|
10.0%
2/20
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Gastrointestinal disorders
Faeces discoloured
|
0.00%
0/20
|
15.0%
3/20
|
23.8%
5/21
|
10.0%
2/20
|
|
Gastrointestinal disorders
Nausea
|
5.0%
1/20
|
10.0%
2/20
|
14.3%
3/21
|
5.0%
1/20
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/21
|
5.0%
1/20
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
1/20
|
0.00%
0/20
|
9.5%
2/21
|
5.0%
1/20
|
|
General disorders
Fatigue
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/21
|
5.0%
1/20
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/21
|
5.0%
1/20
|
|
Infections and infestations
Urinary tract infection
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Investigations
Blood creatine phosphokinase increased
|
5.0%
1/20
|
5.0%
1/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Investigations
Glomuerular filtration rate decreased
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/21
|
5.0%
1/20
|
|
Investigations
Neutrophil count increased
|
0.00%
0/20
|
5.0%
1/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Nervous system disorders
Dizziness
|
0.00%
0/20
|
5.0%
1/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Nervous system disorders
Headache
|
35.0%
7/20
|
25.0%
5/20
|
28.6%
6/21
|
20.0%
4/20
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Psychiatric disorders
Nervousness
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/21
|
5.0%
1/20
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/21
|
5.0%
1/20
|
|
Skin and subcutaneous tissue disorders
Eyelid oedema
|
10.0%
2/20
|
0.00%
0/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/20
|
0.00%
0/20
|
4.8%
1/21
|
0.00%
0/20
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.0%
1/20
|
0.00%
0/20
|
0.00%
0/21
|
0.00%
0/20
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/20
|
0.00%
0/20
|
0.00%
0/21
|
5.0%
1/20
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Written consent
- Publication restrictions are in place
Restriction type: OTHER