Trial Outcomes & Findings for A Study to Evaluate the Effects of Extended Release (ER) Niacin/Laropiprant, Laropiprant, ER Niacin, and Placebo on Urinary Prostanoid Metabolites in Subjects With High Cholesterol (0524A-075)(COMPLETED) (NCT NCT00769132)

Last Updated: 2019-11-21

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

2019-11-21

Participant Flow

Phase I First Patient Entered 16 Aug 2007. Study conducted at Comprehensive Phase One, Miramar, FL. and Cedra Clinical Research LLC, San Antonio, TX.

Participant milestones

Participant milestones
Measure	Sequence 1: D/C/A/B A = Extended Release (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	7	6	6	7
Period 1 COMPLETED	6	6	6	6
Period 1 NOT COMPLETED	1	0	0	1
Period 2 STARTED	6	6	6	6
Period 2 COMPLETED	6	6	6	5
Period 2 NOT COMPLETED	0	0	0	1
Period 3 STARTED	6	6	6	5
Period 3 COMPLETED	5	6	6	5
Period 3 NOT COMPLETED	1	0	0	0
Period 4 STARTED	5	6	6	5
Period 4 COMPLETED	5	5	6	5
Period 4 NOT COMPLETED	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1: D/C/A/B A = Extended Release (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 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	1	0	1
Period 2 Withdrawal by Subject	0	0	1
Period 3 Withdrawal by Subject	1	0	0
Period 4 Withdrawal by Subject	0	1	0

Baseline Characteristics

A Study to Evaluate the Effects of Extended Release (ER) Niacin/Laropiprant, Laropiprant, ER Niacin, and Placebo on Urinary Prostanoid Metabolites in Subjects With High Cholesterol (0524A-075)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Totals for Study n=26 Participants All participants in the study.
Age, Continuous	48.1 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Height	165.5 cm n=5 Participants
Weight	78.4 kg n=5 Participants
urinary 11-dTxB2	418.5 pg/mg creatinine n=5 Participants
urinary PGI2-Metabolite	89.7 pg/mg creatinine n=5 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 4 that were excluded due suspected NSAID/Aspirin use) and had partial data (at least one available period) were included in the 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

Outcome measures
Measure	ER Niacin 2 g / Laropiprant 40 mg n=18 Participants ER niacin 2 g/laropiprant 40 mg daily for 7 days	ER Niacin 2 g n=18 Participants ER niacin 2 g daily for 7 days	Laropiprant 40 mg n=19 Participants Laropiprant 40 mg once daily for 7 days	Placebo n=20 Participants Placebo daily for 7 days
Urinary 11-dehydrothromboxane B2 (11-dTxB2)	414.6 pg/mg creatinine Interval 316.8 to 542.6	371.6 pg/mg creatinine Interval 283.8 to 486.5	407.3 pg/mg creatinine Interval 312.2 to 531.4	466.1 pg/mg creatinine Interval 358.4 to 606.3

SECONDARY outcome

Timeframe: On Day 7 across the 24-hour urinary collection period.

The creatinine-normalized urine levels of PGI-M in the overall 24 hour collection interval following administration on Day 7.

Outcome measures

Outcome measures
Measure	ER Niacin 2 g / Laropiprant 40 mg n=18 Participants ER niacin 2 g/laropiprant 40 mg daily for 7 days	ER Niacin 2 g n=18 Participants ER niacin 2 g daily for 7 days	Laropiprant 40 mg n=19 Participants Laropiprant 40 mg once daily for 7 days	Placebo n=20 Participants Placebo daily for 7 days
Prostaglandin I Metabolite (PGI-M)	73.5 pg/mg creatinine Interval 61.4 to 88.1	70.9 pg/mg creatinine Interval 59.2 to 85.0	114.5 pg/mg creatinine Interval 95.6 to 137.2	127.5 pg/mg creatinine Interval 106.6 to 152.4

Adverse Events

ER Niacin 2 g / Laropiprant 40 mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

ER Niacin 2 g

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Laropiprant 40 mg

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

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

Measure	ER Niacin 2 g / Laropiprant 40 mg n=25 participants at risk ER niacin 2 g/laropiprant 40 mg once daily for 7 days	ER Niacin 2 g n=24 participants at risk ER niacin 2 g once daily for 7 days	Laropiprant 40 mg n=25 participants at risk Laropiprant 40 mg once daily for 7 days	Placebo n=25 participants at risk Placebo once daily for 7 days
Gastrointestinal disorders Gastrointestinal Disorders	28.0% 7/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	29.2% 7/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	12.0% 3/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	12.0% 3/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Gastrointestinal disorders Abdominal Pain	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.3% 2/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Gastrointestinal disorders Constipation	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.3% 2/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Gastrointestinal disorders Diarrhoea	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	12.5% 3/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Gastrointestinal disorders Dry Mouth	12.0% 3/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.2% 1/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Gastrointestinal disorders Nausea	20.0% 5/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	12.5% 3/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Gastrointestinal disorders Vomiting	12.0% 3/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	12.5% 3/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Gastrointestinal disorders General Disorders And Administration Site Conditions	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Musculoskeletal and connective tissue disorders Musculoskeletal And Connective Tissue Disorders	12.0% 3/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.2% 1/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Musculoskeletal and connective tissue disorders Myalgia	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Nervous system disorders Nervous System Disorders	32.0% 8/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	20.8% 5/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	12.0% 3/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Nervous system disorders Headache	28.0% 7/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	16.7% 4/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	12.0% 3/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Renal and urinary disorders Renal And Urinary Disorders	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Skin and subcutaneous tissue disorders Skin And Subcutaneous Tissue Disorders	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	20.8% 5/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Skin and subcutaneous tissue disorders Pruritus	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	20.8% 5/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Skin and subcutaneous tissue disorders Pruritus Generalised	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	0.00% 0/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Vascular disorders Vascular Disorders	32.0% 8/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	83.3% 20/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.
Vascular disorders Flushing	32.0% 8/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	83.3% 20/24 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	8.0% 2/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.	4.0% 1/25 Although 26 participants were included in the assessment of safety, not all participants received all treatments.