Clinical Trial Results:
A Phase II, Multicenter, Open-Label, Noncomparative Study of Raltegravir (MK-0518) in Two Oral Formulations in Combination with Other Antiretroviral Agents to Evaluate the Safety, Tolerability,
and Antiretroviral Activity in HIV-1 Infected Russian Children and Adolescents
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Summary
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EudraCT number |
2017-000050-18 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
11 Dec 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Feb 2017
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First version publication date |
24 Feb 2017
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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-0518-248
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01717287 | ||
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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
11 Dec 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 Dec 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Dec 2013
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This multicenter, open-label, noncomparative study evaluates two oral formulations of raltegravir (MK-0518, film-coated tablet and chewable tablet) in combination with other antiretroviral therapy (ART) for safety, tolerability, and antiretroviral activity in treatment-naïve or treatment-experienced Russian children and adolescents infected with human immunodeficiency virus-1 (HIV-1).
As raltegravir is indicated in combination with other antiretroviral therapies (ARTs) for the treatment of HIV-1 infection in pediatric patients in the United States (US), this study is designed to gain local treatment experience on the use of raltegravir in the pediatric HIV-infected population in Russia.
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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 |
16 Nov 2012
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Long term follow-up planned |
No
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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 |
Russian Federation: 32
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Worldwide total number of subjects |
32
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EEA total number of subjects |
0
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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) |
30
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Adolescents (12-17 years) |
2
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Adults (18-64 years) |
0
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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 |
- | ||||||||||||||||||
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Pre-assignment
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Screening details |
Pediatric (2 to 18 years of age) male and female participants infected with human immunodeficiency virus (HIV) were recruited in the Russian Federation. | ||||||||||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Raltegravir Film-coated Tablet | ||||||||||||||||||
Arm description |
Raltegravir film-coated tablet 400 mg administered by mouth twice per day (b.i.d.) in combination with other anti-retroviral therapy (ART) for 24 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Raltegravir 400 mg film-coated tablet
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Investigational medicinal product code |
MK-0518
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Other name |
ISENTRESS®, MK-0518
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Single 400 mg tablet taken twice daily by mouth.
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Arm title
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Raltegravir Chewable Tablet | ||||||||||||||||||
Arm description |
Raltegravir chewable tablet weight-based dose up to 300 mg administered by mouth b.i.d. in combination with other ART for 24 weeks. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Raltegravir chewable tablet
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Investigational medicinal product code |
MK-0518
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Other name |
ISENTRESS®, MK-0518
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Pharmaceutical forms |
Chewable tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Weight-based dosing up to 300 mg twice daily via 25 mg or 100 mg chewable tablets taken twice daily by mouth.
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Baseline characteristics reporting groups
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Reporting group title |
Raltegravir Film-coated Tablet
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Reporting group description |
Raltegravir film-coated tablet 400 mg administered by mouth twice per day (b.i.d.) in combination with other anti-retroviral therapy (ART) for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Raltegravir Chewable Tablet
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Reporting group description |
Raltegravir chewable tablet weight-based dose up to 300 mg administered by mouth b.i.d. in combination with other ART for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Raltegravir Film-coated Tablet
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Reporting group description |
Raltegravir film-coated tablet 400 mg administered by mouth twice per day (b.i.d.) in combination with other anti-retroviral therapy (ART) for 24 weeks. | ||
Reporting group title |
Raltegravir Chewable Tablet
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Reporting group description |
Raltegravir chewable tablet weight-based dose up to 300 mg administered by mouth b.i.d. in combination with other ART for 24 weeks. | ||
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End point title |
Percentage of Participants Experiencing a Clinical Adverse Event (AE) [1] | ||||||||||||
End point description |
A clinical AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. The all participants as treated population included all enrolled participants who received at least one dose of study drug.
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End point type |
Primary
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End point timeframe |
Up to Week 26
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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: The Sponsor made a business decision to terminate the trial early due to poor enrollment; the decision was not related to any findings regarding the efficacy or safety profile of odanacatib. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants Discontinuing Study Therapy Due to a Clinical AE [2] | ||||||||||||
End point description |
A clinical AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. The all participants as treated population included all enrolled participants who received at least one dose of study drug.
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End point type |
Primary
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End point timeframe |
Up to Week 24
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| Notes [2] - 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: The Sponsor made a business decision to terminate the trial early due to poor enrollment; the decision was not related to any findings regarding the efficacy or safety profile of odanacatib. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants Experiencing a Laboratory AE [3] | ||||||||||||
End point description |
A laboratory AE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. The all participants as treated population included all enrolled participants who received at least one dose of study drug.
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End point type |
Primary
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End point timeframe |
Up to Week 26
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| Notes [3] - 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: The Sponsor made a business decision to terminate the trial early due to poor enrollment; the decision was not related to any findings regarding the efficacy or safety profile of odanacatib. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants Discontinuing Study Therapy Due to a Laboratory AE [4] | ||||||||||||
End point description |
A laboratory AE is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an AE. The all participants as treated population included all enrolled participants who received at least one dose of study drug.
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End point type |
Primary
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End point timeframe |
Up to Week 24
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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: The Sponsor made a business decision to terminate the trial early due to poor enrollment; the decision was not related to any findings regarding the efficacy or safety profile of odanacatib. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in Cluster of Differentiation 4 (CD4) Cell Counts | ||||||||||||
End point description |
This outcome is a measure of immunological response to treatment. The population analyzed included all participants who received at least one dose of study drug and had baseline evaluation.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in CD4 Cell Percentage | ||||||||||||
End point description |
This outcome is a measure of immunological response to treatment. The population analyzed included all participants who received at least one dose of study drug and had baseline evaluation.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants Achieving ≥1 log10 Reduction From Baseline in HIV Ribonucleic Acid (RNA) or Had an HIV RNA Assessment of <200 Copies/mL | ||||||||||||
End point description |
This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL. The full analysis set included all participants who received at least one dose of study drug, had baseline evaluation for those analyses that required baseline data, and had at least one post-baseline evaluation.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants Achieving HIV RNA <40 Copies/mL | ||||||||||||
End point description |
This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL. The full analysis set included all participants who received at least one dose of study drug, had baseline evaluation for those analyses that required baseline data, and had at least one post-baseline evaluation.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants Achieving HIV RNA <200 Copies/mL | ||||||||||||
End point description |
This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL. The full analysis set included all participants who received at least one dose of study drug, had baseline evaluation for those analyses that required baseline data, and had at least one post-baseline evaluation.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to Week 26
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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 |
16.1
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Reporting groups
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Reporting group title |
Raltegravir Chewable Tablet
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Reporting group description |
Raltegravir chewable tablet weight-based dose up to 300 mg administered by mouth twice daily in combination with other ART for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Raltegravir Film-coated Tablet
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Reporting group description |
Raltegravir film-coated tablet 400 mg administered by mouth twice daily in combination with other ART for 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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. | |||
| None reported | |||
