Trial Outcomes & Findings for A Study to Evaluate the Effects of ER Niacin/Laropiprant, Laropiprant, ER Niacin, and Placebo on Urinary Prostanoid Metabolites (0524A-079)(COMPLETED) (NCT NCT00618995)
NCT ID: NCT00618995
Last Updated: 2015-09-07
Results Overview
The creatinine-normalized urine levels of 11-dTxB2 on Day 7 following a 7 day course of daily dosing in the overall 24 hour collection interval
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
26 participants
Primary outcome timeframe
On Day 7 across the 24-hour urinary collection period.
Results posted on
2015-09-07
Participant Flow
Phase I First Patient Enrolled 21 Aug 2007, First Patient Treated 7 Sept 2007. Study conducted at 3 centers: Arkansas Research Medical Testing, LLC, Little Rock, AR; Healthcare Discoveries Inc., San Antonio, TX; and Comprehensive Phase One, Fort Myers, FL. Merck's ER Niacin was used.
Subjects were treated either w/diet and exercise alone, or with metformin, or a sulfonylurea, and had to be on stable meds for \>= 8 wks pre-study.
Participant milestones
| Measure |
Sequence 1: D/C/A/B
A = ER Niacin 2 g/Laropiprant 40 mg once daily for 7 days
B = ER Niacin 2 g once daily for 7 days
C = Laropiprant 40 mg once daily for 7 days
D = Placebo once daily for 7 days
|
Sequence 2: C/B/D/A
A = ER Niacin 2 g/Laropiprant 40 mg once daily for 7 days
B = ER Niacin 2 g once daily for 7 days
C = Laropiprant 40 mg once daily for 7 days
D = Placebo once daily for 7 days
|
Sequence 3: B/A/C/D
A = ER Niacin 2 g/Laropiprant 40 mg once daily for 7 days
B = ER Niacin 2 g once daily for 7 days
C = Laropiprant 40 mg once daily for 7 days
D = Placebo once daily for 7 days
|
Sequence 4: A/D/B/C
A = ER Niacin 2 g/Laropiprant 40 mg once daily for 7 days
B = ER Niacin 2 g once daily for 7 days
C = Laropiprant 40 mg once daily for 7 days
D = Placebo once daily for 7 days
|
|---|---|---|---|---|
|
Period 1
STARTED
|
6
|
7
|
7
|
6
|
|
Period 1
COMPLETED
|
6
|
6
|
5
|
6
|
|
Period 1
NOT COMPLETED
|
0
|
1
|
2
|
0
|
|
Period 2
STARTED
|
6
|
6
|
5
|
6
|
|
Period 2
COMPLETED
|
6
|
6
|
4
|
6
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
1
|
0
|
|
Period 3
STARTED
|
6
|
6
|
4
|
6
|
|
Period 3
COMPLETED
|
6
|
6
|
4
|
6
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
6
|
6
|
4
|
6
|
|
Period 4
COMPLETED
|
5
|
6
|
4
|
6
|
|
Period 4
NOT COMPLETED
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1: D/C/A/B
A = ER Niacin 2 g/Laropiprant 40 mg once daily for 7 days
B = ER Niacin 2 g once daily for 7 days
C = Laropiprant 40 mg once daily for 7 days
D = Placebo once daily for 7 days
|
Sequence 2: C/B/D/A
A = ER Niacin 2 g/Laropiprant 40 mg once daily for 7 days
B = ER Niacin 2 g once daily for 7 days
C = Laropiprant 40 mg once daily for 7 days
D = Placebo once daily for 7 days
|
Sequence 3: B/A/C/D
A = ER Niacin 2 g/Laropiprant 40 mg once daily for 7 days
B = ER Niacin 2 g once daily for 7 days
C = Laropiprant 40 mg once daily for 7 days
D = Placebo once daily for 7 days
|
Sequence 4: A/D/B/C
A = ER Niacin 2 g/Laropiprant 40 mg once daily for 7 days
B = ER Niacin 2 g once daily for 7 days
C = Laropiprant 40 mg once daily for 7 days
D = Placebo once daily for 7 days
|
|---|---|---|---|---|
|
Period 1
Adverse Event
|
0
|
0
|
1
|
0
|
|
Period 1
Protocol Violation
|
0
|
1
|
1
|
0
|
|
Period 2
Protocol Violation
|
0
|
0
|
1
|
0
|
|
Period 4
Adverse Event
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A Study to Evaluate the Effects of ER Niacin/Laropiprant, Laropiprant, ER Niacin, and Placebo on Urinary Prostanoid Metabolites (0524A-079)(COMPLETED)
Baseline characteristics by cohort
| Measure |
Totals For Study
n=26 Participants
All participants in the study.
|
|---|---|
|
Age, Continuous
|
55.3 years
STANDARD_DEVIATION 6.7 • n=39 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=39 Participants
|
|
Height
|
163.9 cm
n=39 Participants
|
|
Weight
|
85.9 kg
n=39 Participants
|
|
urinary 11-dTxB2
|
639.1 pg/mg creatinine
n=39 Participants
|
|
urinary PGI2-Metabolite
|
167.5 pg/mg creatinine
n=39 Participants
|
PRIMARY outcome
Timeframe: On Day 7 across the 24-hour urinary collection period.Population: Twenty-six (26) subjects (including replacements) were enrolled in this study. All available subjects (besides the 2 that were excluded due to suspected NSAID/Aspirin use) who complied with the protocol and had partial data were included in the subsequent statistical analysis models/comparisons.
The creatinine-normalized urine levels of 11-dTxB2 on Day 7 following a 7 day course of daily dosing in the overall 24 hour collection interval
Outcome measures
| Measure |
ER Niacin/Laropiprant
n=22 Participants
Extended Release (ER) Niacin 2 g/Laropiprant 40 mg once daily for 7 days
|
ER Niacin
n=21 Participants
ER Niacin 2 g once daily for 7 days
|
Laropiprant
n=22 Participants
Laropiprant 40 mg once daily for 7 days
|
Placebo
n=22 Participants
Placebo once daily for 7 days
|
|---|---|---|---|---|
|
Urinary 11-Dehydrothromboxane B2 (11-dTxB2)
|
525.3 pg/mg creatinine
Interval 423.8 to 651.1
|
540.8 pg/mg creatinine
Interval 435.0 to 672.3
|
585.3 pg/mg creatinine
Interval 472.2 to 725.4
|
625.1 pg/mg creatinine
Interval 504.3 to 774.8
|
SECONDARY outcome
Timeframe: On Day 7 across the 24-hour urinary collection period.Population: Twenty-six (26) subjects (including replacements) were enrolled in this study. All available subjects (besides the 2 that were excluded due to suspected NSAID/Aspirin use) who complied with the protocol and had partial data were included in the subsequent statistical analysis models/comparisons.
PGI-M in the Overall 24 Hour Collection Interval Following Administration on Day 7
Outcome measures
| Measure |
ER Niacin/Laropiprant
n=22 Participants
Extended Release (ER) Niacin 2 g/Laropiprant 40 mg once daily for 7 days
|
ER Niacin
n=21 Participants
ER Niacin 2 g once daily for 7 days
|
Laropiprant
n=22 Participants
Laropiprant 40 mg once daily for 7 days
|
Placebo
n=22 Participants
Placebo once daily for 7 days
|
|---|---|---|---|---|
|
Prostaglandin I Metabolite (PGI-M)
|
90.1 pg/mg creatinine
Interval 74.5 to 109.0
|
95.4 pg/mg creatinine
Interval 78.7 to 115.5
|
158.5 pg/mg creatinine
Interval 131.0 to 191.8
|
168.1 pg/mg creatinine
Interval 139.0 to 203.4
|
Adverse Events
ER Niacin/Laropiprant
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
ER Niacin
Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths
Laropiprant
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ER Niacin/Laropiprant
n=23 participants at risk
Extended Release (ER) Niacin 2 g/Laropiprant 40 mg once daily for 7 days
|
ER Niacin
n=25 participants at risk
ER Niacin 2 g once daily for 7 days
|
Laropiprant
n=23 participants at risk
Laropiprant 40 mg once daily for 7 days
|
Placebo
n=22 participants at risk
Placebo once daily for 7 days
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/23
|
4.0%
1/25
|
0.00%
0/23
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Acidosis
|
0.00%
0/23
|
4.0%
1/25
|
0.00%
0/23
|
0.00%
0/22
|
Other adverse events
| Measure |
ER Niacin/Laropiprant
n=23 participants at risk
Extended Release (ER) Niacin 2 g/Laropiprant 40 mg once daily for 7 days
|
ER Niacin
n=25 participants at risk
ER Niacin 2 g once daily for 7 days
|
Laropiprant
n=23 participants at risk
Laropiprant 40 mg once daily for 7 days
|
Placebo
n=22 participants at risk
Placebo once daily for 7 days
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/23
|
4.0%
1/25
|
8.7%
2/23
|
0.00%
0/22
|
|
Gastrointestinal disorders
Abdominal Distension
|
4.3%
1/23
|
12.0%
3/25
|
0.00%
0/23
|
0.00%
0/22
|
|
Gastrointestinal disorders
Abdominal Pain
|
4.3%
1/23
|
4.0%
1/25
|
8.7%
2/23
|
9.1%
2/22
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/23
|
0.00%
0/25
|
0.00%
0/23
|
9.1%
2/22
|
|
Gastrointestinal disorders
Constipation
|
4.3%
1/23
|
12.0%
3/25
|
13.0%
3/23
|
4.5%
1/22
|
|
Gastrointestinal disorders
Diarrhoea
|
8.7%
2/23
|
8.0%
2/25
|
13.0%
3/23
|
22.7%
5/22
|
|
Gastrointestinal disorders
Dyspepsia
|
4.3%
1/23
|
12.0%
3/25
|
4.3%
1/23
|
9.1%
2/22
|
|
Gastrointestinal disorders
Nausea
|
17.4%
4/23
|
36.0%
9/25
|
13.0%
3/23
|
9.1%
2/22
|
|
Gastrointestinal disorders
Vomiting
|
4.3%
1/23
|
16.0%
4/25
|
4.3%
1/23
|
4.5%
1/22
|
|
General disorders
Asthenia
|
0.00%
0/23
|
8.0%
2/25
|
8.7%
2/23
|
0.00%
0/22
|
|
General disorders
Feeling Hot
|
4.3%
1/23
|
8.0%
2/25
|
0.00%
0/23
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/23
|
0.00%
0/25
|
8.7%
2/23
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
4.3%
1/23
|
8.0%
2/25
|
0.00%
0/23
|
0.00%
0/22
|
|
Nervous system disorders
Burning Sensation
|
8.7%
2/23
|
24.0%
6/25
|
0.00%
0/23
|
0.00%
0/22
|
|
Nervous system disorders
Dizziness
|
4.3%
1/23
|
12.0%
3/25
|
4.3%
1/23
|
0.00%
0/22
|
|
Nervous system disorders
Headache
|
13.0%
3/23
|
24.0%
6/25
|
17.4%
4/23
|
18.2%
4/22
|
|
Nervous system disorders
Paraesthesia
|
8.7%
2/23
|
16.0%
4/25
|
0.00%
0/23
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Erythema
|
13.0%
3/23
|
24.0%
6/25
|
0.00%
0/23
|
4.5%
1/22
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
30.4%
7/23
|
56.0%
14/25
|
8.7%
2/23
|
13.6%
3/22
|
|
Vascular disorders
Flushing
|
30.4%
7/23
|
68.0%
17/25
|
0.00%
0/23
|
0.00%
0/22
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER