We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00769132
Recruitment Status : Completed
First Posted : October 8, 2008
Results First Posted : November 27, 2008
Last Update Posted : November 21, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hypercholesterolemia
Interventions Drug: Comparator: niacin + laropiprant
Drug: Comparator: niacin
Drug: Comparator: laropiprant
Drug: Comparator: placebo
Enrollment 26
Recruitment Details

Phase I

First Patient Entered 16 Aug 2007.

Study conducted at Comprehensive Phase One, Miramar, FL. and Cedra Clinical Research LLC, San Antonio, TX.

Pre-assignment Details  
Arm/Group Title Sequence 1: D/C/A/B Sequence 2: C/B/D/A Sequence 3: B/A/C/D Sequence 4: A/D/B/C
Hide Arm/Group Description

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

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

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

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 Title: Period 1
Started 7 6 6 7
Completed 6 6 6 6
Not Completed 1 0 0 1
Reason Not Completed
Adverse Event             1             0             0             1
Period Title: Period 2
Started 6 6 6 6
Completed 6 6 6 5
Not Completed 0 0 0 1
Reason Not Completed
Withdrawal by Subject             0             0             0             1
Period Title: Period 3
Started 6 6 6 5
Completed 5 6 6 5
Not Completed 1 0 0 0
Reason Not Completed
Withdrawal by Subject             1             0             0             0
Period Title: Period 4
Started 5 6 6 5
Completed 5 5 6 5
Not Completed 0 1 0 0
Reason Not Completed
Withdrawal by Subject             0             1             0             0
Arm/Group Title Totals for Study
Hide Arm/Group Description All participants in the study.
Overall Number of Baseline Participants 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants
48.1  (11.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Female
14
  53.8%
Male
12
  46.2%
Height  
Mean (Full Range)
Unit of measure:  Cm
Number Analyzed 26 participants
165.5
(147.0 to 185.0)
Weight  
Mean (Full Range)
Unit of measure:  Kg
Number Analyzed 26 participants
78.4
(58.0 to 102.9)
urinary 11-dTxB2   [1] 
Median (Full Range)
Unit of measure:  Pg/mg creatinine
Number Analyzed 26 participants
418.5
(142.0 to 783.1)
[1]
Measure Description: urinary levels of 11-dehydrothromboxane B2 (24 hour collection)
urinary PGI2-Metabolite   [1] 
Median (Full Range)
Unit of measure:  Pg/mg creatinine
Number Analyzed 26 participants
89.7
(45.2 to 242.9)
[1]
Measure Description: urinary levels of 2,3-dinor 6-keto-PGF1a (Prostaglandin I-M) 24-hour collection
1.Primary Outcome
Title Urinary 11-dehydrothromboxane B2 (11-dTxB2)
Hide Description 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.
Time Frame On Day 7 across the 24-hour urinary collection period.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title ER Niacin 2 g / Laropiprant 40 mg ER Niacin 2 g Laropiprant 40 mg Placebo
Hide Arm/Group Description:
ER niacin 2 g/laropiprant 40 mg daily for 7 days
ER niacin 2 g daily for 7 days
Laropiprant 40 mg once daily for 7 days
Placebo daily for 7 days
Overall Number of Participants Analyzed 18 18 19 20
Least Squares Mean (95% Confidence Interval)
Unit of Measure: pg/mg creatinine
414.6
(316.8 to 542.6)
371.6
(283.8 to 486.5)
407.3
(312.2 to 531.4)
466.1
(358.4 to 606.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g / Laropiprant 40 mg, ER Niacin 2 g
Comments The endpoint is the urine levels of 11-dTxB2 on Day 7 following a 7 day course of daily dosing in the overall 24 hour collection interval. The point estimate and 90% confidence intervals (CIs) were calculated for the geometric mean ratio (GMR) [Treatment A/B] of the urine levels of 11-dTxB2 on Day 7.
Type of Statistical Test Non-Inferiority or Equivalence (legacy)
Comments Two treatments are comparable if the geometric mean ratio is contained within the interval [0.50-2.00].
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 1.12
Confidence Interval 90%
0.9 to 1.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Laropiprant 40 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 0.87
Confidence Interval 90%
0.71 to 1.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 0.8
Confidence Interval 90%
0.65 to 0.98
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g / Laropiprant 40 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 0.89
Confidence Interval 90%
0.72 to 1.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g, Laropiprant 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 0.91
Confidence Interval 90%
0.74 to 1.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g / Laropiprant 40 mg, Laropiprant 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 1.02
Confidence Interval 90%
0.83 to 1.25
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Prostaglandin I Metabolite (PGI-M)
Hide Description The creatinine-normalized urine levels of PGI-M in the overall 24 hour collection interval following administration on Day 7.
Time Frame On Day 7 across the 24-hour urinary collection period.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title ER Niacin 2 g / Laropiprant 40 mg ER Niacin 2 g Laropiprant 40 mg Placebo
Hide Arm/Group Description:
ER niacin 2 g/laropiprant 40 mg daily for 7 days
ER niacin 2 g daily for 7 days
Laropiprant 40 mg once daily for 7 days
Placebo daily for 7 days
Overall Number of Participants Analyzed 18 18 19 20
Least Squares Mean (95% Confidence Interval)
Unit of Measure: pg/mg creatinine
73.5
(61.4 to 88.1)
70.9
(59.2 to 85.0)
114.5
(95.6 to 137.2)
127.5
(106.6 to 152.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g / Laropiprant 40 mg, ER Niacin 2 g
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 1.04
Confidence Interval 90%
0.92 to 1.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Laropiprant 40 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 0.9
Confidence Interval 90%
0.8 to 1.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 0.56
Confidence Interval 90%
0.49 to 0.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g / Laropiprant 40 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 0.58
Confidence Interval 90%
0.51 to 0.65
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g, Laropiprant 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 0.62
Confidence Interval 90%
0.55 to 0.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection ER Niacin 2 g / Laropiprant 40 mg, Laropiprant 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric least-squares mean ratio
Estimated Value 0.64
Confidence Interval 90%
0.57 to 0.72
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description Although 26 participants were included in the assessment of safety, not all participants received all treatments.
 
Arm/Group Title ER Niacin 2 g / Laropiprant 40 mg ER Niacin 2 g Laropiprant 40 mg Placebo
Hide Arm/Group Description ER niacin 2 g/laropiprant 40 mg once daily for 7 days ER niacin 2 g once daily for 7 days Laropiprant 40 mg once daily for 7 days Placebo once daily for 7 days
All-Cause Mortality
ER Niacin 2 g / Laropiprant 40 mg ER Niacin 2 g Laropiprant 40 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
ER Niacin 2 g / Laropiprant 40 mg ER Niacin 2 g Laropiprant 40 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)   0/24 (0.00%)   0/25 (0.00%)   0/25 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ER Niacin 2 g / Laropiprant 40 mg ER Niacin 2 g Laropiprant 40 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/25 (60.00%)   21/24 (87.50%)   4/25 (16.00%)   5/25 (20.00%) 
Gastrointestinal disorders         
Gastrointestinal Disorders  7/25 (28.00%)  7/24 (29.17%)  3/25 (12.00%)  3/25 (12.00%) 
Abdominal Pain  1/25 (4.00%)  2/24 (8.33%)  1/25 (4.00%)  0/25 (0.00%) 
Constipation  1/25 (4.00%)  2/24 (8.33%)  2/25 (8.00%)  0/25 (0.00%) 
Diarrhoea  0/25 (0.00%)  3/24 (12.50%)  1/25 (4.00%)  1/25 (4.00%) 
Dry Mouth  3/25 (12.00%)  1/24 (4.17%)  0/25 (0.00%)  1/25 (4.00%) 
Nausea  5/25 (20.00%)  3/24 (12.50%)  1/25 (4.00%)  1/25 (4.00%) 
Vomiting  3/25 (12.00%)  3/24 (12.50%)  2/25 (8.00%)  0/25 (0.00%) 
General Disorders And Administration Site Conditions  2/25 (8.00%)  0/24 (0.00%)  2/25 (8.00%)  1/25 (4.00%) 
Musculoskeletal and connective tissue disorders         
Musculoskeletal And Connective Tissue Disorders  3/25 (12.00%)  1/24 (4.17%)  2/25 (8.00%)  2/25 (8.00%) 
Myalgia  2/25 (8.00%)  0/24 (0.00%)  1/25 (4.00%)  0/25 (0.00%) 
Nervous system disorders         
Nervous System Disorders  8/25 (32.00%)  5/24 (20.83%)  2/25 (8.00%)  3/25 (12.00%) 
Headache  7/25 (28.00%)  4/24 (16.67%)  1/25 (4.00%)  3/25 (12.00%) 
Renal and urinary disorders         
Renal And Urinary Disorders  0/25 (0.00%)  0/24 (0.00%)  1/25 (4.00%)  2/25 (8.00%) 
Skin and subcutaneous tissue disorders         
Skin And Subcutaneous Tissue Disorders  2/25 (8.00%)  5/24 (20.83%)  1/25 (4.00%)  0/25 (0.00%) 
Pruritus  1/25 (4.00%)  5/24 (20.83%)  1/25 (4.00%)  0/25 (0.00%) 
Pruritus Generalised  2/25 (8.00%)  0/24 (0.00%)  0/25 (0.00%)  0/25 (0.00%) 
Vascular disorders         
Vascular Disorders  8/25 (32.00%)  20/24 (83.33%)  2/25 (8.00%)  1/25 (4.00%) 
Flushing  8/25 (32.00%)  20/24 (83.33%)  2/25 (8.00%)  1/25 (4.00%) 
1
Term from vocabulary, MedDRA (10.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT00769132    
Other Study ID Numbers: 0524A-075
2008_561
First Submitted: October 7, 2008
First Posted: October 8, 2008
Results First Submitted: October 30, 2008
Results First Posted: November 27, 2008
Last Update Posted: November 21, 2019