Clinical Trial Results:
A Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled, 12-Week Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Lipid-Lowering Therapy in Adult Patients with Homozygous Familial Hypercholesterolemia (HoFH)
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Summary
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EudraCT number |
2012-002434-37 |
Trial protocol |
GB NO CZ IT |
Global end of trial date |
05 Jun 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Apr 2016
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First version publication date |
29 Jul 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MK-0859-042
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01841684 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Jun 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Jun 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Jun 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
This study will evaluate the safety and effect of anacetrapib on low-density lipoprotein-cholesterol (LDL-C) when added to ongoing lipid-lowering therapy. The primary hypothesis is that treatment with anacetrapib 100 mg for 12 weeks will lower LDL-C to a greater extent than treatment with placebo.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Jun 2013
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
3 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Norway: 2
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Worldwide total number of subjects |
2
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
2
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Study was terminated due to lack of enrollment after 2 participants were randomized. No planned efficay or safety analyses were performed due to low sample number. | |||||||||||||||
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Pre-assignment
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Screening details |
Male or female (not of child bearing potential) and 18 years of age or older diagnosed with HoFH by genotyping. Other inclusion and exclusion criteria applied. | |||||||||||||||
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Period 1
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Period 1 title |
Treatment Period (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Anacetrapib | |||||||||||||||
Arm description |
Participants receive anacetrapib 100 mg orally once daily for 12 weeks. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Anacetrapib
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Investigational medicinal product code |
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Other name |
MK-0859
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
one 100 mg tablet orally once daily for 12 weeks.
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Arm title
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Placebo | |||||||||||||||
Arm description |
Participants received placebo for anacetrapib once daily for 12 weeks | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
one placebo tablet orally once daily for 12 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Anacetrapib
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Reporting group description |
Participants receive anacetrapib 100 mg orally once daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo for anacetrapib once daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Anacetrapib
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Reporting group description |
Participants receive anacetrapib 100 mg orally once daily for 12 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo for anacetrapib once daily for 12 weeks | ||
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End point title |
Percent change from Baseline in Low-density Lipoprotein-Cholesterol (LDL-C) using beta-quantification method [1] | ||||||||||||
End point description |
LDL-C levels measured at baseline and after 12 weeks of treatment using beta quantification method
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End point type |
Primary
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End point timeframe |
Baseline and Week 12
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Study terminated early. No planned statistical analyses were performed. |
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| Notes [2] - Study terminated early. No planned analyses were performed. [3] - Study terminated early. No planned analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants with Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) Consecutive Elevations ≥3x Upper Limit of Normal (ULN) [4] | |||||||||
End point description |
Participants had AST and ALT levels assessed throughout the 12 week treatment period. Participants who had 2 consecutive assessments of either AST or ALT that were 3 x ULN or greater were recorded. The AST UNLs for males and females were 43 U/L and 36 U/L, respectively. The ALT UNLs for males and females were 40 U/L and 33 U/L, respectively.
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Study terminated early. No planned statistical analyses were performed. |
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| Notes [5] - Study terminated early. No planned analyses were performed. [6] - Study terminated early. No planned analyses were performed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants with Creatine Phosphokinase Elevations ≥10xULN with or without Muscle Symptoms [7] | |||||||||
End point description |
Participants had creatine phosphokinase (CPK) assessed throughout the 12 week treatment period. Participants who had any CPK level that was >=10 x ULN and had associated muscle spasms were recorded. The UNLs for males and females were 207 U/L and 169 U/L, respectively.
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Study terminated early. No planned statistical analyses were performed. |
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| Notes [8] - Study terminated early. No planned analyses were performed. [9] - Study terminated early. No planned analyses were performed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants with Sodium, Chloride, or Bicarbonate Elevations >ULN or Potassium Levels < Lower Limit of Normal (LLN) [10] | |||||||||
End point description |
Participants had sodium, chloride, bicarbonate, and potassium levels assessed throughout the 12 week treatment period. Participants who had any sodium chloride, or bicarbonate levels that was > the ULN or had a potassium level < LLN were summarized. The ULNs for sodium, chloride, and bicarbonate were 145 mEq/L, 110 mEq/L, and 33 mEq/L, respectively. The LLN for potassium was 3.5 mEq/L.
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Study terminated early. No planned statistical analyses were performed. |
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| Notes [11] - Study terminated early. No planned analyses were performed. [12] - Study terminated early. No planned analyses were performed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants with Pre-specified Adjudicated Cardiovascular Serious Adverse Events or Death from Any Cause [13] | |||||||||
End point description |
An AE or suspected adverse reaction was considered an SAE if it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or acongenital anomaly/birth defect. All events were adjudicated by an expert committee independent of the Sponsor. Participants that experienced adjudicated SAEs of CV death, non-fatal stroke, non-fatal myocardial infarction, or unstable angina or died from any cause were recorded.
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Study terminated early. No planned statistical analyses were performed. |
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| Notes [14] - Study terminated early. No planned analyses were performed. [15] - Study terminated early. No planned analyses were performed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants with Significant Increase in Blood Pressure [16] | |||||||||
End point description |
Sitting blood pressure was assessed throughout the 12 week treatment period. Participants with an increase in sitting systolic blood pressure (SiSBP) of ≥10 mmHg and/or ≥15 mmHg and/or an increase in sitting diastolic blood pressure (SiSBP) of ≥10 mmHg were recorded.
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End point type |
Primary
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End point timeframe |
12 weeks
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| Notes [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Study terminated early. No planned statistical analyses were performed. |
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| Notes [17] - Study terminated early. No planned analyses were performed. [18] - Study terminated early. No planned analyses were performed. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Percent Change from Baseline in High-density Lipoprotein-cholesterol (HDL-C) | ||||||||||||
End point description |
HDL-C levels measured at baseline and after 12 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| Notes [19] - Study terminated early. No planned analyses were performed. [20] - Study terminated early. No planned analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percent Change from Baseline in Apolipoprotein A-I (apoA-I) | ||||||||||||
End point description |
Apo A-1 levels measured at baseline and after 12 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| Notes [21] - Study terminated early. No planned analyses were performed. [22] - Study terminated early. No planned analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
up to 12 weeks
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
All participants who received at least one dose of placebo. | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Anacetrapib 100 mg
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Reporting group description |
All participants who received at least one dose of Anacetrapib 100 mg | |||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: None of the participants experienced a non-serious adverse event. |
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 May 2013 |
Amendment 1: provided new data on the pharmacokinetic (PK) properties of anacetrapib and related changes to eligibility criteria. The 52-week open label extension phase was removed from the study and a 12-week follow-up period was added. The addition of serial PK measurements during the follow-up period was to be performed to determine the accumulation and clearance of the compound in the HoFH population. |
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20 Nov 2013 |
Amendment 3: removed the 30% cap limiting the number of participants being treated with LDL apheresis that were allowed to enroll in the trial. All participants who were receiving LDL apheresis treatment for at least 8 weeks prior to randomization were allowed to enter the study. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Study was terminated early due to poor enrollment after 2 participants were randomly assigned to a treatment arm and dosed. No planned analyses were performed. | |||
