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

MK0524A Bioequivalence Study (0524A-059)

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: NCT00944645
Recruitment Status : Completed
First Posted : July 23, 2009
Results First Posted : November 25, 2009
Last Update Posted : June 19, 2015
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Dyslipidemia
Interventions Drug: niacin (+) laropiprant (Source 1)
Drug: Comparator: niacin (+) laropiprant (Source 2)
Enrollment 188
Recruitment Details  
Pre-assignment Details  
Arm/Group Title MK0524A Phase III Tablet Then MK0524A New Site Tablet MK0524A New Site Tablet Then MK0524A Phase III Tablet
Hide Arm/Group Description MK0524A Phase III tablet: MK0524A (1000 mg ER Niacin/20 mg MK0524) Phase III tablet (Source 1)/MK0524A New Site tablet: MK0524A (1000 mg ER Niacin/20 mg MK0524) tablet from new manufacturing site (Source 2) MK0524A New Site tablet: MK0524A (1000 mg ER Niacin/20 mg MK0524) tablet from new manufacturing site (Source 2)/ MK0524A Phase III tablet: MK0524A (1000 mg ER Niacin/20 mg MK0524) Phase III tablet (Source 1)
Period Title: Period 1
Started 94 94
Completed 94 94
Not Completed 0 0
Period Title: Period 2
Started 94 94
Completed 86 85
Not Completed 8 9
Reason Not Completed
Adverse Event             1             0
Lost to Follow-up             0             3
Withdrawal by Subject             7             6
Arm/Group Title All Participants
Hide Arm/Group Description Includes all participants from Both treatment groups; MK0524A Phase III tablet and MK0524A New Site tablet
Overall Number of Baseline Participants 188
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 188 participants
38.5
(18 to 65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 188 participants
Female
92
  48.9%
Male
96
  51.1%
Height  
Mean (Full Range)
Unit of measure:  Centimeters
Number Analyzed 188 participants
166.6
(140 to 190)
Weight  
Mean (Full Range)
Unit of measure:  Kilograms
Number Analyzed 188 participants
71.6
(48.4 to 101)
1.Primary Outcome
Title Maximum Plasma Concentration (Cmax) of Nicotinuric Acid
Hide Description Measure of rate of absorption of ER niacin
Time Frame Predose and up to 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
The Hodges-Lehmann estimator was used to analyze nicotinuric acid Cmax and uses only subjects with data available on both treatment periods. 188 subjects were randomized,17 subjects discontinued, 26 subjects were inadvertently overdosed with 5 tablets of MK0524A 1000 mg/20 mg, reducing the available subject population for analysis to 145.
Arm/Group Title MK0524A New Site Tablet MK0524A Phase III Tablet
Hide Arm/Group Description:
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
Overall Number of Participants Analyzed 145 145
Median (Inter-Quartile Range)
Unit of Measure: ng/mL
1190
(956 to 1610)
1260
(948 to 1660)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MK0524A New Site Tablet, MK0524A Phase III Tablet
Comments

MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) tablet from new manufacturing site (Source 2)

MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) Phase III tablet (Source 1)

Type of Statistical Test Non-Inferiority or Equivalence
Comments Primary research hypothesis I: The Cmax of nicotinuric acid (NUA) following the administration of MK0524A (ER niacin 1000 mg/ laropiprant 20 mg) tablets from 2 manufacturing sites is similar (i.e., the true GMR of NUA Cmax is contained within the bioequivalence interval (0.80, 1.25)).
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.98
Confidence Interval 90%
0.93 to 1.03
Estimation Comments [Not Specified]
2.Primary Outcome
Title Total Amount of Urinary Excretion of Niacin and Its Metabolites
Hide Description Measure of extent of absorption of ER niacin
Time Frame Predose and up to 96 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
A linear mixed effect model was used to analyze total amount of urinary excretion of niacin and its metabolite and uses data available from at least one treatment period. 157 subjects had data from the treatment of MK0524A New Site Tablet, and 161 subjects had data from the treatment of MK0524A Phase III Tablet
Arm/Group Title MK0524A New Site Tablet MK0524A Phase III Tablet
Hide Arm/Group Description:
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
Overall Number of Participants Analyzed 157 161
Median (Standard Deviation)
Unit of Measure: micro mole
5280  (1894) 5470  (1330)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MK0524A New Site Tablet, MK0524A Phase III Tablet
Comments

MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) tablet from new manufacturing site (Source 2)

MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) Phase III tablet (Source 1)

Type of Statistical Test Non-Inferiority or Equivalence
Comments Primary research hypothesis II: The total urinary excretion of niacin and niacin metabolites following the administration of MK0524 (ER niacin 1000 mg/ laropiprant 20 mg) tablets from 2 manufacturing sites is similar (i.e., the true GMR of total urinary excretion of niacin and its metabolites is contained within the bioequivalence interval (0.80, 1.25)).
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 0.94
Confidence Interval 90%
0.89 to 0.98
Estimation Comments [Not Specified]
3.Primary Outcome
Title Area Under Curve (AUC 0-infinity) of Laropiprant
Hide Description Measure of extent of absorption of laropiprant
Time Frame Predose and up to 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
A linear mixed effect model was used to analyze laropiprant AUC0-infinity and uses data available from at least one treatment period. 166 subjects had data from the treatment of MK0524A New Site Tablet, and 167 subjects had data from the treatment of MK0524A Phase III Tablet
Arm/Group Title MK0524A New Site Tablet MK0524A Phase III Tablet
Hide Arm/Group Description:
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
Overall Number of Participants Analyzed 166 167
Median (Standard Deviation)
Unit of Measure: Micro Molar times Hour
6.36  (3.01) 6.37  (2.66)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MK0524A New Site Tablet, MK0524A Phase III Tablet
Comments

Group B: MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) tablet from new manufacturing site (Source 2)

Group A: MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) Phase III tablet (Source 1)

Type of Statistical Test Non-Inferiority or Equivalence
Comments Primary research hypothesis III: The AUC0-infinity of laropiprant following the administration of MK0524A (ER niacin 1000 mg/ laropiprant 20 mg) tablets from 2 manufacturing sites is similar (i.e., the true GMR of MK0524 AUC0-∞ is contained within the bioequivalence interval (0.80, 1.25)).
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.00
Confidence Interval 95%
0.95 to 1.05
Estimation Comments [Not Specified]
4.Primary Outcome
Title Maximum Concentration (Cmax) of Laropiprant
Hide Description Measure of rate of absorption of laropiprant
Time Frame Predose and up to 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
A linear mixed effect model was used to analyze laropiprant Cmax and uses data available from at least one treatment period. 166 subjects had data from the treatment of MK0524A New Site Tablet, and 167 subjects had data from the treatment of MK0524A Phase III Tablet.
Arm/Group Title MK0524A New Site Tablet MK0524A Phase III Tablet
Hide Arm/Group Description:
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
Overall Number of Participants Analyzed 166 167
Median (Standard Deviation)
Unit of Measure: micro Molar
0.988  (0.563) 0.975  (0.466)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MK0524A New Site Tablet, MK0524A Phase III Tablet
Comments

MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) tablet from new manufacturing site (Source 2)

MK0524A (1000 mg ER Niacin/20 mg MK-laropiprant) Phase III tablet (Source 1)

Type of Statistical Test Non-Inferiority or Equivalence
Comments Primary research hypothesis IV: The Cmax of laropiprant following the administration of MK0524A (ER niacin 1000 mg/ laropiprant 20 mg) tablets from 2 manufacturing sites is similar (i.e., the true GMR of MK0524 Cmax is contained within the bioequivalence interval (0.80, 1.25)).
Method of Estimation Estimation Parameter Geometric Mean Ratio
Estimated Value 1.02
Confidence Interval 95%
0.96 to 1.09
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title MK0524A Phase III Tablet MK0524A New Site Tablet
Hide Arm/Group Description MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1) MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
All-Cause Mortality
MK0524A Phase III Tablet MK0524A New Site Tablet
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
MK0524A Phase III Tablet MK0524A New Site Tablet
Affected / at Risk (%) Affected / at Risk (%)
Total   0/188 (0.00%)   2/188 (1.06%) 
Gastrointestinal disorders     
Hematemesis * 1  0/188 (0.00%)  1/188 (0.53%) 
Nervous system disorders     
Syncope * 1  0/188 (0.00%)  1/188 (0.53%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
MK0524A Phase III Tablet MK0524A New Site Tablet
Affected / at Risk (%) Affected / at Risk (%)
Total   98/188 (52.13%)   100/188 (53.19%) 
Cardiac disorders     
Palpitations * 1  1/188 (0.53%)  2/188 (1.06%) 
Tachycardia * 1  2/188 (1.06%)  0/188 (0.00%) 
Ear and labyrinth disorders     
Ear Discomfort * 1  0/188 (0.00%)  1/188 (0.53%) 
Eye disorders     
Eye Irritation * 1  1/188 (0.53%)  0/188 (0.00%) 
Eye Pain * 1  0/188 (0.00%)  1/188 (0.53%) 
Vision Blurred * 1  1/188 (0.53%)  1/188 (0.53%) 
Gastrointestinal disorders     
Abdominal Discomfort * 1  1/188 (0.53%)  0/188 (0.00%) 
Abdominal Pain * 1  3/188 (1.60%)  4/188 (2.13%) 
Abdominal Pain Upper * 1  0/188 (0.00%)  3/188 (1.60%) 
Cheilitis * 1  1/188 (0.53%)  0/188 (0.00%) 
Constipation * 1  1/188 (0.53%)  0/188 (0.00%) 
Defaecation Urgency * 1  0/188 (0.00%)  1/188 (0.53%) 
Diarrhoea * 1  3/188 (1.60%)  11/188 (5.85%) 
Dyspepsia * 1  1/188 (0.53%)  0/188 (0.00%) 
Epigastric Discomfort * 1  1/188 (0.53%)  2/188 (1.06%) 
Eructation * 1  1/188 (0.53%)  0/188 (0.00%) 
Flatulence * 1  2/188 (1.06%)  1/188 (0.53%) 
Gastritis * 1  1/188 (0.53%)  1/188 (0.53%) 
Gastrooesophageal Reflux Disease * 1  2/188 (1.06%)  2/188 (1.06%) 
Haematochezia * 1  1/188 (0.53%)  0/188 (0.00%) 
Haemorrhoids * 1  1/188 (0.53%)  0/188 (0.00%) 
Nausea * 1  13/188 (6.91%)  11/188 (5.85%) 
Rectal Haemorrhage * 1  2/188 (1.06%)  0/188 (0.00%) 
Vomiting * 1  4/188 (2.13%)  6/188 (3.19%) 
General disorders     
Chest Discomfort * 1  1/188 (0.53%)  0/188 (0.00%) 
Chills * 1  1/188 (0.53%)  1/188 (0.53%) 
Fatigue * 1  1/188 (0.53%)  1/188 (0.53%) 
Influenza Like Illness * 1  1/188 (0.53%)  0/188 (0.00%) 
Pyrexia * 1  1/188 (0.53%)  0/188 (0.00%) 
Infections and infestations     
Herpes Simplex * 1  0/188 (0.00%)  1/188 (0.53%) 
Rhinitis * 1  1/188 (0.53%)  1/188 (0.53%) 
Viral Infection * 1  1/188 (0.53%)  0/188 (0.00%) 
Injury, poisoning and procedural complications     
Excoriation * 1  1/188 (0.53%)  1/188 (0.53%) 
Fall * 1  1/188 (0.53%)  0/188 (0.00%) 
Head Injury * 1  1/188 (0.53%)  0/188 (0.00%) 
Overdose * 1  12/188 (6.38%)  14/188 (7.45%) 
Post Procedural Haematoma * 1  0/188 (0.00%)  1/188 (0.53%) 
Skin Laceration * 1  0/188 (0.00%)  1/188 (0.53%) 
Investigations     
Aspartate Aminotransferase Increased * 1  0/188 (0.00%)  1/188 (0.53%) 
Blood Amylase Increased * 1  0/188 (0.00%)  1/188 (0.53%) 
Haemoglobin Decreased * 1  1/188 (0.53%)  0/188 (0.00%) 
Helicobacter Pylori Identification Test Positive * 1  1/188 (0.53%)  0/188 (0.00%) 
Lipase Increased * 1  0/188 (0.00%)  1/188 (0.53%) 
Occult Blood Positive * 1  0/188 (0.00%)  1/188 (0.53%) 
Metabolism and nutrition disorders     
Hyperglycaemia * 1  1/188 (0.53%)  0/188 (0.00%) 
Polydipsia * 1  1/188 (0.53%)  0/188 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  1/188 (0.53%)  0/188 (0.00%) 
Back Pain * 1  2/188 (1.06%)  2/188 (1.06%) 
Flank Pain * 1  1/188 (0.53%)  0/188 (0.00%) 
Muscle Spasms * 1  0/188 (0.00%)  1/188 (0.53%) 
Muscular Weakness * 1  0/188 (0.00%)  1/188 (0.53%) 
Musculoskeletal Pain * 1  0/188 (0.00%)  1/188 (0.53%) 
Myalgia * 1  3/188 (1.60%)  1/188 (0.53%) 
Neck Pain * 1  2/188 (1.06%)  1/188 (0.53%) 
Pain In Extremity * 1  0/188 (0.00%)  1/188 (0.53%) 
Nervous system disorders     
Dizziness * 1  10/188 (5.32%)  7/188 (3.72%) 
Headache * 1  15/188 (7.98%)  20/188 (10.64%) 
Paraesthesia * 1  16/188 (8.51%)  16/188 (8.51%) 
Syncope * 1  2/188 (1.06%)  0/188 (0.00%) 
Psychiatric disorders     
Anxiety * 1  1/188 (0.53%)  1/188 (0.53%) 
Insomnia * 1  0/188 (0.00%)  1/188 (0.53%) 
Renal and urinary disorders     
Bladder Pain * 1  1/188 (0.53%)  0/188 (0.00%) 
Haematuria * 1  1/188 (0.53%)  0/188 (0.00%) 
Reproductive system and breast disorders     
Dysmenorrhoea * 1  0/188 (0.00%)  1/188 (0.53%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  0/188 (0.00%)  1/188 (0.53%) 
Nasal Congestion * 1  0/188 (0.00%)  2/188 (1.06%) 
Pharyngolaryngeal Pain * 1  2/188 (1.06%)  0/188 (0.00%) 
Rhinorrhoea * 1  2/188 (1.06%)  1/188 (0.53%) 
Skin and subcutaneous tissue disorders     
Erythema * 1  0/188 (0.00%)  2/188 (1.06%) 
Pruritus * 1  20/188 (10.64%)  19/188 (10.11%) 
Pruritus Generalised * 1  1/188 (0.53%)  0/188 (0.00%) 
Vascular disorders     
Flushing * 1  69/188 (36.70%)  70/188 (37.23%) 
Vasodilatation * 1  7/188 (3.72%)  5/188 (2.66%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 10.0
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: NCT00944645    
Other Study ID Numbers: 0524A-059
MK0524A-059
2009_613
First Submitted: July 21, 2009
First Posted: July 23, 2009
Results First Submitted: October 20, 2009
Results First Posted: November 25, 2009
Last Update Posted: June 19, 2015