Trial Outcomes & Findings for Study to Investigate the Efficacy and Pharmacokinetic Profile of K-877-ER Compared to K-877-IR (NCT NCT04447820)
NCT ID: NCT04447820
Last Updated: 2023-12-22
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
96 participants
Primary outcome timeframe
Baseline to Day 28
Results posted on
2023-12-22
Participant Flow
The Screening Period occurred no more than 70 days and no less than 7 days prior to the first dose of study drug. The up to 10-week Screening Period allowed for a 6-week washout period, if needed, followed by an up to 4-week Qualification Period that was used to assess patient eligibility. Prior to treatment on Day 1, eligible patients were randomized in a 1:1:1 ratio to 1 of 3 treatment groups. Randomization was stratified by sex, statin use, and PK assessment.
Participant milestones
| Measure |
K-877-IR
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
Overall Study
STARTED
|
32
|
32
|
32
|
|
Overall Study
COMPLETED
|
31
|
31
|
29
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Investigate the Efficacy and Pharmacokinetic Profile of K-877-ER Compared to K-877-IR
Baseline characteristics by cohort
| Measure |
K-877-IR
n=32 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=32 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=32 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
Total
n=96 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
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
72 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
44 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
52 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
72 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 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
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
31 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
93 Participants
n=4 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
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Statin Use
Yes
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
|
Statin Use
No
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
|
TG at Baseline
|
278.72 mg/dL
STANDARD_DEVIATION 53.316 • n=5 Participants
|
294.88 mg/dL
STANDARD_DEVIATION 61.949 • n=7 Participants
|
307.35 mg/dL
STANDARD_DEVIATION 73.575 • n=5 Participants
|
293.65 mg/dL
STANDARD_DEVIATION 63.915 • n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to Day 28Population: The Per-Protocol Set (PPS) was defined as all patients in the Full Analysis Set without any major protocol deviations and who had baseline and Day 28 fasting serum TG measurements.
Outcome measures
| Measure |
K-877-IR
n=31 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=30 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=27 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
Estimated Percentage Change in Fasting Triglyceride(s) (TG)
|
-41.57 Percent Change
Standard Deviation 3.295
|
-36.79 Percent Change
Standard Deviation 3.319
|
-38.94 Percent Change
Standard Deviation 3.553
|
SECONDARY outcome
Timeframe: Baseline to Day 28Outcome measures
| Measure |
K-877-IR
n=31 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=30 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=27 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
Percentage Change From Baseline to Day 28 in Total Cholesterol (TC)
|
-6.07 Percent Change
Standard Deviation 15.417
|
-8.68 Percent Change
Standard Deviation 13.266
|
0.28 Percent Change
Standard Deviation 18.100
|
SECONDARY outcome
Timeframe: Baseline to Day 28Population: PPS
Outcome measures
| Measure |
K-877-IR
n=31 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=30 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=27 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
Percentage Change From Baseline to Day 28 in Low-density Lipoprotein Cholesterol (LDL-C)
|
3.56 Percent Change
Standard Deviation 28.586
|
-2.16 Percent Change
Standard Deviation 21.394
|
22.71 Percent Change
Standard Deviation 64.420
|
SECONDARY outcome
Timeframe: Baseline to Day 28Population: PPS
Outcome measures
| Measure |
K-877-IR
n=31 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=30 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=27 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
Percentage Change From Baseline to Day 28 in High-density Lipoprotein Cholesterol (HDL-C)
|
12.22 Percent Change
Standard Deviation 27.335
|
15.39 Percent Change
Standard Deviation 18.190
|
20.04 Percent Change
Standard Deviation 24.370
|
SECONDARY outcome
Timeframe: Baseline to Day 28Population: PPS
Outcome measures
| Measure |
K-877-IR
n=31 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=30 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=27 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
Percentage Change From Baseline to Day 28 in Remnant Cholesterol
|
-33.85 Percentage Change
Standard Deviation 32.467
|
-30.08 Percentage Change
Standard Deviation 25.394
|
-32.34 Percentage Change
Standard Deviation 24.761
|
SECONDARY outcome
Timeframe: Baseline to Day 28Population: PPS
Outcome measures
| Measure |
K-877-IR
n=31 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=30 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=27 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
Percentage Change From Baseline to Day 28 in Non-HDL-C
|
-10.04 Percent Change
Standard Deviation 21.704
|
-11.12 Percent Change
Standard Deviation 18.847
|
-3.74 Percent Change
Standard Deviation 21.394
|
SECONDARY outcome
Timeframe: Baseline to Day 28Population: PPS
Outcome measures
| Measure |
K-877-IR
n=31 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=30 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=27 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
Percentage Change From Baseline to Day 28 in Free Fatty Acid (FFAs)
|
-7.35 Percent Change
Standard Deviation 45.110
|
-17.17 Percent Change
Standard Deviation 25.430
|
-10.22 Percent Change
Standard Deviation 40.436
|
SECONDARY outcome
Timeframe: Day 28Population: The PK Analysis Set included all patients from the Safety Analysis Set who had at least 1 PK sample.
Observed maximum measured plasma concentration (Cmax)
Outcome measures
| Measure |
K-877-IR
n=6 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=8 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=7 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
K-877 PK Parameters Cmax
|
2.061 ng/mL
Geometric Coefficient of Variation 63.9
|
2.746 ng/mL
Geometric Coefficient of Variation 85.2
|
5.433 ng/mL
Geometric Coefficient of Variation 61.2
|
SECONDARY outcome
Timeframe: Day 28Population: The PK Analysis Set included all patients from the Safety Analysis Set who had at least 1 PK sample.
Outcome measures
| Measure |
K-877-IR
n=5 Participants
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=8 Participants
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=7 Participants
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
K-877 PK Parameters AUC (Tau)
|
10.239 h-ng/mL
Geometric Coefficient of Variation 43.1
|
22.566 h-ng/mL
Geometric Coefficient of Variation 71.3
|
41.611 h-ng/mL
Geometric Coefficient of Variation 44.1
|
Adverse Events
K-877-IR
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
K-877-ER Dose A
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
K-877-ER Dose B
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 |
K-877-IR
n=32 participants at risk
K-877 Immediate release (IR) tablet orally twice daily (BID) from day 1 through 28.
|
K-877-ER Dose A
n=32 participants at risk
K-877 Extended release (ER) tablet (Dose A) orally once daily (QD) from day 1 through 28.
|
K-877-ER Dose B
n=32 participants at risk
K-877 Extended release (ER) tablets (Dose B) orally once daily (QD) from day 1 through 28.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/32 • 28 Days
1. The Safety Analysis Set was defined as all randomized participants who received at least 1 dose of the randomized study drug. 2. Treatment-emergent AEs (TEAEs) were defined as AEs that occurred for the first time after the first dose of study drug or existed prior to the first dose and worsened during the Treatment Period.
|
3.1%
1/32 • 28 Days
1. The Safety Analysis Set was defined as all randomized participants who received at least 1 dose of the randomized study drug. 2. Treatment-emergent AEs (TEAEs) were defined as AEs that occurred for the first time after the first dose of study drug or existed prior to the first dose and worsened during the Treatment Period.
|
6.2%
2/32 • 28 Days
1. The Safety Analysis Set was defined as all randomized participants who received at least 1 dose of the randomized study drug. 2. Treatment-emergent AEs (TEAEs) were defined as AEs that occurred for the first time after the first dose of study drug or existed prior to the first dose and worsened during the Treatment Period.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/32 • 28 Days
1. The Safety Analysis Set was defined as all randomized participants who received at least 1 dose of the randomized study drug. 2. Treatment-emergent AEs (TEAEs) were defined as AEs that occurred for the first time after the first dose of study drug or existed prior to the first dose and worsened during the Treatment Period.
|
0.00%
0/32 • 28 Days
1. The Safety Analysis Set was defined as all randomized participants who received at least 1 dose of the randomized study drug. 2. Treatment-emergent AEs (TEAEs) were defined as AEs that occurred for the first time after the first dose of study drug or existed prior to the first dose and worsened during the Treatment Period.
|
9.4%
3/32 • 28 Days
1. The Safety Analysis Set was defined as all randomized participants who received at least 1 dose of the randomized study drug. 2. Treatment-emergent AEs (TEAEs) were defined as AEs that occurred for the first time after the first dose of study drug or existed prior to the first dose and worsened during the Treatment Period.
|
Additional Information
Director, Clinical Operations
Kowa Research Institute, Inc.
Phone: 919-433-1600
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place