Trial Outcomes & Findings for MK0524A Bioequivalence Study (0524A-059) (NCT NCT00944645)
NCT ID: NCT00944645
Last Updated: 2015-06-19
Results Overview
Measure of rate of absorption of ER niacin
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
188 participants
Primary outcome timeframe
Predose and up to 24 hours postdose
Results posted on
2015-06-19
Participant Flow
Participant milestones
| Measure |
MK0524A Phase III Tablet Then MK0524A New Site Tablet
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 Then MK0524A Phase III Tablet
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 1
STARTED
|
94
|
94
|
|
Period 1
COMPLETED
|
94
|
94
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
94
|
94
|
|
Period 2
COMPLETED
|
86
|
85
|
|
Period 2
NOT COMPLETED
|
8
|
9
|
Reasons for withdrawal
| Measure |
MK0524A Phase III Tablet Then MK0524A New Site Tablet
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 Then MK0524A Phase III Tablet
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 2
Adverse Event
|
1
|
0
|
|
Period 2
Lost to Follow-up
|
0
|
3
|
|
Period 2
Withdrawal by Subject
|
7
|
6
|
Baseline Characteristics
MK0524A Bioequivalence Study (0524A-059)
Baseline characteristics by cohort
| Measure |
All Participants
n=188 Participants
Includes all participants from Both treatment groups; MK0524A Phase III tablet and MK0524A New Site tablet
|
|---|---|
|
Age, Continuous
|
38.5 years
FULL_RANGE 1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
92 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
96 Participants
n=5 Participants
|
|
Height
|
166.6 Centimeters
n=5 Participants
|
|
Weight
|
71.6 Kilograms
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and up to 24 hours postdosePopulation: 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.
Measure of rate of absorption of ER niacin
Outcome measures
| Measure |
MK0524A New Site Tablet
n=145 Participants
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
|
MK0524A Phase III Tablet
n=145 Participants
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Nicotinuric Acid
|
1190 ng/mL
Interval 956.0 to 1610.0
|
1260 ng/mL
Interval 948.0 to 1660.0
|
PRIMARY outcome
Timeframe: Predose and up to 96 hours postdosePopulation: 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
Measure of extent of absorption of ER niacin
Outcome measures
| Measure |
MK0524A New Site Tablet
n=157 Participants
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
|
MK0524A Phase III Tablet
n=161 Participants
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
|
|---|---|---|
|
Total Amount of Urinary Excretion of Niacin and Its Metabolites
|
5280 micro mole
Standard Deviation 1894
|
5470 micro mole
Standard Deviation 1330
|
PRIMARY outcome
Timeframe: Predose and up to 48 hours postdosePopulation: 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
Measure of extent of absorption of laropiprant
Outcome measures
| Measure |
MK0524A New Site Tablet
n=166 Participants
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
|
MK0524A Phase III Tablet
n=167 Participants
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
|
|---|---|---|
|
Area Under Curve (AUC 0-infinity) of Laropiprant
|
6.36 Micro Molar times Hour
Standard Deviation 3.01
|
6.37 Micro Molar times Hour
Standard Deviation 2.66
|
PRIMARY outcome
Timeframe: Predose and up to 48 hours postdosePopulation: 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.
Measure of rate of absorption of laropiprant
Outcome measures
| Measure |
MK0524A New Site Tablet
n=166 Participants
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
|
MK0524A Phase III Tablet
n=167 Participants
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
|
|---|---|---|
|
Maximum Concentration (Cmax) of Laropiprant
|
0.988 micro Molar
Standard Deviation 0.563
|
0.975 micro Molar
Standard Deviation 0.466
|
Adverse Events
MK0524A Phase III Tablet
Serious events: 0 serious events
Other events: 98 other events
Deaths: 0 deaths
MK0524A New Site Tablet
Serious events: 2 serious events
Other events: 100 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MK0524A Phase III Tablet
n=188 participants at risk
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
|
MK0524A New Site Tablet
n=188 participants at risk
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
|
|---|---|---|
|
Gastrointestinal disorders
Hematemesis
|
0.00%
0/188
|
0.53%
1/188
|
|
Nervous system disorders
Syncope
|
0.00%
0/188
|
0.53%
1/188
|
Other adverse events
| Measure |
MK0524A Phase III Tablet
n=188 participants at risk
MK0524A (1000 mg ER Niacin/20 mg laropiprant) Phase III tablet (Source 1)
|
MK0524A New Site Tablet
n=188 participants at risk
MK0524A (1000 mg ER Niacin/20 mg laropiprant) tablet from new manufacturing site (Source 2)
|
|---|---|---|
|
Cardiac disorders
Palpitations
|
0.53%
1/188
|
1.1%
2/188
|
|
Cardiac disorders
Tachycardia
|
1.1%
2/188
|
0.00%
0/188
|
|
Ear and labyrinth disorders
Ear Discomfort
|
0.00%
0/188
|
0.53%
1/188
|
|
Eye disorders
Eye Irritation
|
0.53%
1/188
|
0.00%
0/188
|
|
Eye disorders
Eye Pain
|
0.00%
0/188
|
0.53%
1/188
|
|
Eye disorders
Vision Blurred
|
0.53%
1/188
|
0.53%
1/188
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.53%
1/188
|
0.00%
0/188
|
|
Gastrointestinal disorders
Abdominal Pain
|
1.6%
3/188
|
2.1%
4/188
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/188
|
1.6%
3/188
|
|
Gastrointestinal disorders
Cheilitis
|
0.53%
1/188
|
0.00%
0/188
|
|
Gastrointestinal disorders
Constipation
|
0.53%
1/188
|
0.00%
0/188
|
|
Gastrointestinal disorders
Defaecation Urgency
|
0.00%
0/188
|
0.53%
1/188
|
|
Gastrointestinal disorders
Diarrhoea
|
1.6%
3/188
|
5.9%
11/188
|
|
Gastrointestinal disorders
Dyspepsia
|
0.53%
1/188
|
0.00%
0/188
|
|
Gastrointestinal disorders
Epigastric Discomfort
|
0.53%
1/188
|
1.1%
2/188
|
|
Gastrointestinal disorders
Eructation
|
0.53%
1/188
|
0.00%
0/188
|
|
Gastrointestinal disorders
Flatulence
|
1.1%
2/188
|
0.53%
1/188
|
|
Gastrointestinal disorders
Gastritis
|
0.53%
1/188
|
0.53%
1/188
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
1.1%
2/188
|
1.1%
2/188
|
|
Gastrointestinal disorders
Haematochezia
|
0.53%
1/188
|
0.00%
0/188
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.53%
1/188
|
0.00%
0/188
|
|
Gastrointestinal disorders
Nausea
|
6.9%
13/188
|
5.9%
11/188
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
1.1%
2/188
|
0.00%
0/188
|
|
Gastrointestinal disorders
Vomiting
|
2.1%
4/188
|
3.2%
6/188
|
|
General disorders
Chest Discomfort
|
0.53%
1/188
|
0.00%
0/188
|
|
General disorders
Chills
|
0.53%
1/188
|
0.53%
1/188
|
|
General disorders
Fatigue
|
0.53%
1/188
|
0.53%
1/188
|
|
General disorders
Influenza Like Illness
|
0.53%
1/188
|
0.00%
0/188
|
|
General disorders
Pyrexia
|
0.53%
1/188
|
0.00%
0/188
|
|
Infections and infestations
Herpes Simplex
|
0.00%
0/188
|
0.53%
1/188
|
|
Infections and infestations
Rhinitis
|
0.53%
1/188
|
0.53%
1/188
|
|
Infections and infestations
Viral Infection
|
0.53%
1/188
|
0.00%
0/188
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.53%
1/188
|
0.53%
1/188
|
|
Injury, poisoning and procedural complications
Fall
|
0.53%
1/188
|
0.00%
0/188
|
|
Injury, poisoning and procedural complications
Head Injury
|
0.53%
1/188
|
0.00%
0/188
|
|
Injury, poisoning and procedural complications
Overdose
|
6.4%
12/188
|
7.4%
14/188
|
|
Injury, poisoning and procedural complications
Post Procedural Haematoma
|
0.00%
0/188
|
0.53%
1/188
|
|
Injury, poisoning and procedural complications
Skin Laceration
|
0.00%
0/188
|
0.53%
1/188
|
|
Investigations
Aspartate Aminotransferase Increased
|
0.00%
0/188
|
0.53%
1/188
|
|
Investigations
Blood Amylase Increased
|
0.00%
0/188
|
0.53%
1/188
|
|
Investigations
Haemoglobin Decreased
|
0.53%
1/188
|
0.00%
0/188
|
|
Investigations
Helicobacter Pylori Identification Test Positive
|
0.53%
1/188
|
0.00%
0/188
|
|
Investigations
Lipase Increased
|
0.00%
0/188
|
0.53%
1/188
|
|
Investigations
Occult Blood Positive
|
0.00%
0/188
|
0.53%
1/188
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.53%
1/188
|
0.00%
0/188
|
|
Metabolism and nutrition disorders
Polydipsia
|
0.53%
1/188
|
0.00%
0/188
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.53%
1/188
|
0.00%
0/188
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
1.1%
2/188
|
1.1%
2/188
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
0.53%
1/188
|
0.00%
0/188
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
0.00%
0/188
|
0.53%
1/188
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
0.00%
0/188
|
0.53%
1/188
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/188
|
0.53%
1/188
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.6%
3/188
|
0.53%
1/188
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
1.1%
2/188
|
0.53%
1/188
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
0.00%
0/188
|
0.53%
1/188
|
|
Nervous system disorders
Dizziness
|
5.3%
10/188
|
3.7%
7/188
|
|
Nervous system disorders
Headache
|
8.0%
15/188
|
10.6%
20/188
|
|
Nervous system disorders
Paraesthesia
|
8.5%
16/188
|
8.5%
16/188
|
|
Nervous system disorders
Syncope
|
1.1%
2/188
|
0.00%
0/188
|
|
Psychiatric disorders
Anxiety
|
0.53%
1/188
|
0.53%
1/188
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/188
|
0.53%
1/188
|
|
Renal and urinary disorders
Bladder Pain
|
0.53%
1/188
|
0.00%
0/188
|
|
Renal and urinary disorders
Haematuria
|
0.53%
1/188
|
0.00%
0/188
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/188
|
0.53%
1/188
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/188
|
0.53%
1/188
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
0.00%
0/188
|
1.1%
2/188
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
|
1.1%
2/188
|
0.00%
0/188
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
1.1%
2/188
|
0.53%
1/188
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/188
|
1.1%
2/188
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.6%
20/188
|
10.1%
19/188
|
|
Skin and subcutaneous tissue disorders
Pruritus Generalised
|
0.53%
1/188
|
0.00%
0/188
|
|
Vascular disorders
Flushing
|
36.7%
69/188
|
37.2%
70/188
|
|
Vascular disorders
Vasodilatation
|
3.7%
7/188
|
2.7%
5/188
|
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