A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)

Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT02748057
Collaborator
(none)
135
2
18.8

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

Study Type:
Interventional
Actual Enrollment :
135 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III, Open-label, Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Patients With Hypercholesterolemia Who Have Inadequate LDL-C Control on Ezetimibe or Rosuvastatin Monotherapy
Actual Study Start Date :
May 18, 2016
Actual Primary Completion Date :
Dec 11, 2017
Actual Study Completion Date :
Dec 11, 2017

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

  1. 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.

  2. 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

  1. 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

Ages Eligible for Study:
20 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT02748057
Other Study ID Numbers:
  • 0653H-833
  • 163314
  • MK-0653H-833
First Posted:
Apr 22, 2016
Last Update Posted:
Feb 9, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:

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

1. Primary Outcome
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%
2. Primary Outcome
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%
3. Secondary Outcome
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

[Not Specified]

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
Email ClinicalTrialsDisclosure@merck.com
Responsible Party:
Organon and Co
ClinicalTrials.gov Identifier:
NCT02748057
Other Study ID Numbers:
  • 0653H-833
  • 163314
  • MK-0653H-833
First Posted:
Apr 22, 2016
Last Update Posted:
Feb 9, 2022
Last Verified:
Feb 1, 2022