A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653C in Japanese Participants With Hypercholesterolemia (MK-0653C-384)

Phase 3

Completed

• Conditions: Heterozygous Familial Hypercholesterolemia; Hypercholesterolemia
• Interventions: Drug: EZ 10 mg/Atorva 10 mg FDC; Drug: EZ 10 mg/Atorva 20 mg FDC

• Registration Number: NCT02460159
• Lead Sponsor: Organon and Co

Brief Summary

This study will assess the safety and tolerability of Ezetimibe (EZ) 10 mg/Atorvastatin (Atora) 10 mg and EZ 10mg/Atora 20 mg fixed-dose combination (FDC) in Japanese participants with hypercholesterolemia uncontrolled with monotherapy of Ezetimibe 10 mg or Atorvastatin up to 20 mg. There is no formal hypothesis for the study.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-05-29
• Study First Submitted QC: 2015-05-29
• Study First Posted: 2015-06-02
• Study Start: 2015-06-23
• Primary Completion: 2016-12-22
• Study Completion: 2016-12-22
• Results First Submitted: 2017-12-14
• Results First Submitted QC: 2017-12-14
• Results First Posted: 2018-01-11
• Status Verified: 2022-02
• Last Update Submitted: 2024-05-08
• Last Update Posted: 2024-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EZ 10 mg/Atorva 10 mg FDC	EZ 10 mg/Atorva 10 mg FDC	one EZ 10 mg/Atorva 10 mg fixed-dose combination (FDC) tablet orally with food once daily for 52 weeks.
EZ 10 mg/Atorva 20 mg FDC	EZ 10 mg/Atorva 20 mg FDC	one EZ 10 mg/Atorva 20 mg fixed -dose combination (FDC) tablet orally with food once daily for 52 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experience 1 or More Gastrointestinal-related AEs	up to 54 weeks	Gastrointestinal-related AEs included all preferred terms within system organ class of Gastrointestinal Disorders except Chapped Lips and Toothache.
Percentage of Participants Who Experience 1 or More Hepatitis-related AEs	up to 54 weeks	Hepatitis-related AEs included Cholestasis, Cytolytic Hepatitis, Hepatic Cyst, Hepatic Failure, Hepatic Lesion, Hepatic Necrosis, Hepatitis, Hepatitis Cholestatic, Hepatitis Fulminant, Hepatitis Infectious, Hepatocellular Injury, Hepatomegaly, Jaundice, Jaundice Cholestatic.
Percentage of Participants Who Experience Elevations in ALT or AST ≥10 Times ULN	up to 52 weeks	Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had assessments of ALT and/or AST that were 10x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Percentage of Participants Who Experience 1 or More Adverse Event (AE)	up to 54 Weeks	An AE was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized.
Percentage of Participants Who Experience 1 or More Gallbladder-related AEs	up to 54 weeks	Gallbladder-related AEs included Bile Duct Obstruction, Bile Duct Stone, Bile Duct Stenosis, Biliary Colic, Cholangitis, Cholecystectomy, Cholecystitis, Cholelithiasis, Gallbladder Disorder, Gallbladder Perforation, Hepatic Pain, and Hydrocholecystis.
Percentage of Participants Who Experience Consecutive Elevations in Alanine Aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) ≥3 Times Upper Normal Limit (ULN)	up to 52 weeks	Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had 2 consecutive assessments of ALT and/or AST that were 3 x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Percentage of Participants Who Experience Elevations in ALT or AST ≥5 Times ULN	up to 52 weeks	Participants had ALT and AST levels assessed throughout the 52 week treatment period. Participants who had assessments of ALT or AST that were 5x ULN or greater were recorded. The ALT and AST ULNs were 40 U/L.
Percentage of Participants Who Experience 1 or More Allergic Reaction or Rash AEs	up to 54 weeks	Allergic Reaction or Rash AEs included Allergy to Arthropod Sting, Anaphylactoid Reaction, Anaphylactic Reaction, Anaphylatic Shock, Anaphylactoid Shock, Angioedema, Conjunctivitis Allergic, Contrast Media Reaction, Dermatitis, Dermatitis Allergic, Dermatitis Atopic, Dermatitis Bullous, Dermatitis Contact, Dermatitis Psoriasiform, Drug Hypersensitivity, Eczema, Eosinophila, Erythema, Eye Allergy, Face Oedema, Hypersensitivity, Mechanical Urticaria, Palmar Erythema, Periorbital Oedema, Photodermatosis, Photosensitivity Allergic reaction, Photosensitivity Reaction, Pigmentation Disorder, Pruritus, Pruritus Generalised, Rash, Rash Erythematous, Rash Follicular, Rash Generalised, Rash Maculo-Papular, Rash Papulosquamous, Rash Pruritic, Rash Pustular, Rash Vesicular, Rhinitis, Rhinitis Allergic, Rosacea, Skin Exfoliation, Skin Disorder, Skin Hyperpigmentation, Skin Lesion, Skin Mass, Skin Ulcer, Subcutaneous Nodule, Swelling Face, Systemic Lupus Erythematosus Rash, Urticaria.
Percentage of Participants With Potential Hy's Law Condition	up to 52 weeks	Percentage of Participants with Potential Hy's Law Condition (defined as serum ALT or serum AST elevations \>3xULN, with serum alkaline phosphatase \<2xULN and total bilirubin (TBL) ≥2xULN) was summarized. The ALT and AST ULNs were 40 U/L. The ULN for alkaline phosphatase was 359 IU/L and the ULN for total bilirubin was 1.2 mg/dL.
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN With Muscle Symptoms	up to 52 weeks	Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN	up to 52 weeks	Participants had creatine phosphokinase (CK) levels assessed throughout the 12 week treatment period. Participants who had any CK level that was ≥10 x ULN were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.
Percentage of Participants Who Experience Elevations in Creatine Kinase (CK) ≥10 Times ULN and Drug-Related Muscle Symptoms	up to 52 weeks	Participants had CK levels assessed throughout the 52 week treatment period. Participants who had any CK level that was ≥10 x ULN and had associated muscle symptoms present within +/- 7 days that were reported as at least possibly-related to study drug were recorded. The CK ULNs for males and females were 287 IU/L and 163 IU/L, respectively.