A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
Study Details
Study Description
Brief Summary
The study will assess the safety and tolerability of Ezetimibe 10 mg+ Rosuvastatin 2.5 mg and Ezetimibe 10 mg+ Rosuvastatin 5.0 mg for up to 52 weeks in Japanese participants with hypercholesterolemia uncontrolled with monotherapy of Ezetimibe 10 mg or Rosuvastatin up to 5 mg.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Ezetimibe 10 mg + Rosuvastatin 2.5 mg 1 Ezetimibe 10 mg tablet and 1 Rosuvastatin 2.5 mg capsule/tablet orally, once daily for 52 weeks. If participant does not achieve low-density lipoprotein- cholesterol (LDL-C) goal after Week 12, dosage of Rosuvastatin may be increased to 5.0 mg |
Drug: Ezetimibe
Drug: Rosuvastatin
|
Experimental: Ezetimibe 10 mg + Rosuvastatin 5.0 mg 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules/tablets orally, once daily for 52 weeks. |
Drug: Ezetimibe
Drug: Rosuvastatin
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Who Experience at Least 1 Adverse Event (AE) [Up to 2 weeks post last dose of study drug (up to 54 weeks)]
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who reported at least 1 AE was summarized.
- Percentage of Participants Who Had Study Drug Discontinued Due to an AE [up to 52 weeks]
An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who had study drug discontinued due to an AE was summarized.
Secondary Outcome Measures
- Percentage Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) [Baseline (predose) and Week 52]
Blood was collected at baseline (predose) and after 52 weeks of treatment to determine LDL-C levels. LDL-C was calculated using the Friedewald equation. If triglycerides (TG) exceeded 400 mg/dL (4.6 mmol/L), LDL-C was determined by beta quantification ultracentrifugation. The percentage change from baseline at Week 52 was summarized.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Japanese
-
Outpatient with hypercholesterolemia
-
Female participant who is of reproductive potential has to agree to remain abstinent or use (or partner use) two acceptable methods of birth control from date of signed informed consent to the 14 days after the last dose of study drug
-
Will maintain a stable diet that is consistent with the Japan Atherosclerosis Society Guideline 2012 (JAS 2012) for prevention of atherosclerotic cardiovascular diseases for the duration of the study
Exclusion Criteria:
-
Uncontrolled hypertension (treated or untreated)
-
Uncontrolled type 1 or type 2 diabetes mellitus
-
Homozygous Familial Hypercholesterolemia or has undergone low-density lipoprotein (LDL) apheresis
-
Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins
-
Has had a gastrointestinal tract bypass, or other significant intestinal malabsorption
-
History of cancer within the past 5 years (except for successfully treated dermatological basal cell or squamous cell carcinoma or in situ cervical cancer)
-
Human Immunodeficiency Virus (HIV) positive
-
History of drug/alcohol abuse within the past 5 years or psychiatric illness not adequately controlled and stable on pharmacotherapy
-
Consumes more than 25 g of alcohol per day
-
Currently following an excessive weight reduction diet
-
Currently engages in a vigorous exercise regimen (e.g.; marathon training, body building training etc.) or intends to start training during the study
-
Hypersensitivity or intolerance to Ezetimibe or Rosuvastatin
-
Myopathy or rhabdomyolysis with Ezetimibe or any statin
-
Pregnant or lactating
-
Taking any other investigational drugs and/or has taken any investigational drugs within 30 days
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Organon and Co
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Publications
None provided.- 0653H-833
- 163314
- MK-0653H-833
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg |
---|---|---|
Arm/Group Description | 1 Ezetimibe 10 mg tablet and 1 Rosuvastatin 2.5 mg capsule/tablet orally, once daily for 52 weeks. If participant does not achieve low-density lipoprotein-cholesterol (LDL-C) goal after Week 12, dosage of Rosuvastatin may have been increased to 5.0 mg | 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules/tablets orally, once daily for 52 weeks. |
Period Title: Overall Study | ||
STARTED | 114 | 21 |
COMPLETED | 109 | 19 |
NOT COMPLETED | 5 | 2 |
Baseline Characteristics
Arm/Group Title | Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg | Total |
---|---|---|---|
Arm/Group Description | 1 Ezetimibe 10 mg tablet and 1 Rosuvastatin 2.5 mg capsule/tablet orally, once daily for 52 weeks. If participant does not achieve low-density lipoprotein-cholesterol (LDL-C) goal after Week 12, dosage of Rosuvastatin may have been increased to 5.0 mg | 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules/tablets orally, once daily for 52 weeks. | Total of all reporting groups |
Overall Participants | 114 | 21 | 135 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
58.2
(10.8)
|
52.4
(13.3)
|
57.3
(11.4)
|
Sex: Female, Male (Count of Participants) | |||
Female |
61
53.5%
|
9
42.9%
|
70
51.9%
|
Male |
53
46.5%
|
12
57.1%
|
65
48.1%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
Not Hispanic or Latino |
114
100%
|
21
100%
|
135
100%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
Title | Percentage of Participants Who Experience at Least 1 Adverse Event (AE) |
---|---|
Description | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who reported at least 1 AE was summarized. |
Time Frame | Up to 2 weeks post last dose of study drug (up to 54 weeks) |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received at least 1 dose of study drug during treatment period. |
Arm/Group Title | Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg |
---|---|---|
Arm/Group Description | 1 Ezetimibe 10 mg tablet and 1 Rosuvastatin 2.5 mg capsule/tablet orally, once daily for 52 weeks. If participant does not achieve low-density lipoprotein-cholesterol (LDL-C) goal after Week 12, dosage of Rosuvastatin may have been increased to 5.0 mg | 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules/tablets orally, once daily for 52 weeks. |
Measure Participants | 114 | 21 |
Number [Percentage of Participants] |
72.8
63.9%
|
76.2
362.9%
|
Title | Percentage of Participants Who Had Study Drug Discontinued Due to an AE |
---|---|
Description | An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants who had study drug discontinued due to an AE was summarized. |
Time Frame | up to 52 weeks |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received at least 1 dose of study drug during treatment period. |
Arm/Group Title | Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg |
---|---|---|
Arm/Group Description | 1 Ezetimibe 10 mg tablet and 1 Rosuvastatin 2.5 mg capsule/tablet orally, once daily for 52 weeks. If participant does not achieve low-density lipoprotein-cholesterol (LDL-C) goal after Week 12, dosage of Rosuvastatin may have been increased to 5.0 mg | 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules/tablets orally, once daily for 52 weeks. |
Measure Participants | 114 | 21 |
Number [Percentage of Participants] |
0.9
0.8%
|
0.0
0%
|
Title | Percentage Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) |
---|---|
Description | Blood was collected at baseline (predose) and after 52 weeks of treatment to determine LDL-C levels. LDL-C was calculated using the Friedewald equation. If triglycerides (TG) exceeded 400 mg/dL (4.6 mmol/L), LDL-C was determined by beta quantification ultracentrifugation. The percentage change from baseline at Week 52 was summarized. |
Time Frame | Baseline (predose) and Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
All participants that received at least 1 dose of study drug, had baseline data for those analyses that required baseline data and had post-baseline data for endpoint. |
Arm/Group Title | Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg |
---|---|---|
Arm/Group Description | 1 Ezetimibe 10 mg tablet and 1 Rosuvastatin 2.5 mg capsule/tablet orally, once daily for 52 weeks. If participant does not achieve low-density lipoprotein-cholesterol (LDL-C) goal after Week 12, dosage of Rosuvastatin may have been increased to 5.0 mg | 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules/tablets orally, once daily for 52 weeks. |
Measure Participants | 108 | 17 |
Mean (95% Confidence Interval) [Percentage change] |
-33.8
|
-23.9
|
Adverse Events
Time Frame | Up to 2 weeks post last dose of study drug (up to 54 weeks) | |||
---|---|---|---|---|
Adverse Event Reporting Description | Population included all participants who received at least 1 dose of study drug during treatment period. | |||
Arm/Group Title | Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg | ||
Arm/Group Description | 1 Ezetimibe 10 mg tablet and 1 Rosuvastatin 2.5 mg capsule/tablet orally, once daily for 52 weeks. If participant does not achieve low-density lipoprotein-cholesterol (LDL-C) goal after Week 12, dosage of Rosuvastatin may have been increased to 5.0 mg | 1 Ezetimibe 10 mg tablet and 2 Rosuvastatin 2.5 mg capsules/tablets orally, once daily for 52 weeks. | ||
All Cause Mortality |
||||
Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/114 (0%) | 0/21 (0%) | ||
Serious Adverse Events |
||||
Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/114 (1.8%) | 1/21 (4.8%) | ||
Musculoskeletal and connective tissue disorders | ||||
Intervertebral disc protrusion | 0/114 (0%) | 0 | 1/21 (4.8%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Intestinal adenocarcinoma | 1/114 (0.9%) | 1 | 0/21 (0%) | 0 |
Psychiatric disorders | ||||
Anxiety disorder | 1/114 (0.9%) | 1 | 0/21 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Ezetimibe 10 mg + Rosuvastatin 2.5 mg | Ezetimibe 10 mg + Rosuvastatin 5.0 mg | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 53/114 (46.5%) | 13/21 (61.9%) | ||
Infections and infestations | ||||
Gastroenteritis | 8/114 (7%) | 8 | 1/21 (4.8%) | 2 |
Nasopharyngitis | 41/114 (36%) | 69 | 8/21 (38.1%) | 18 |
Rhinitis | 1/114 (0.9%) | 1 | 2/21 (9.5%) | 2 |
Injury, poisoning and procedural complications | ||||
Contusion | 2/114 (1.8%) | 2 | 2/21 (9.5%) | 3 |
Investigations | ||||
Liver function test abnormal | 3/114 (2.6%) | 3 | 2/21 (9.5%) | 2 |
Metabolism and nutrition disorders | ||||
Type 2 diabetes mellitus | 3/114 (2.6%) | 3 | 2/21 (9.5%) | 2 |
Musculoskeletal and connective tissue disorders | ||||
Back pain | 9/114 (7.9%) | 11 | 1/21 (4.8%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Name/Title | Senior Vice President, Global Clinical Development |
---|---|
Organization | Merck Sharp & Dohme Corp. |
Phone | 1-800-672-6372 |
ClinicalTrialsDisclosure@merck.com |
- 0653H-833
- 163314
- MK-0653H-833