Clinical Trial Results:
A Phase IIa, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Worldwide, Proof-of-Concept Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 in Subjects with Active Rheumatoid Arthritis and an Inadequate Response or Intolerance to Anti-TNF-α Therapy
Summary
|
|
EudraCT number |
2012-002181-12 |
Trial protocol |
SE GB ES DK GR IT HU AT |
Global end of trial date |
08 Oct 2013
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
31 Mar 2016
|
First version publication date |
13 Jun 2015
|
Other versions |
v1 |
Version creation reason |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
8457-010
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01651936 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Merck Sharp & Dohme Corp.
|
||
Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
|
||
Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
|
||
Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
08 Oct 2013
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
08 Oct 2013
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
08 Oct 2013
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
This study assessed the safety and efficacy of MK-8457 in participants with active rheumatoid arthritis (RA) and an inadequate response or intolerance to anti-tumor necrosis factor α (anti-TNF-α) therapy. The primary hypothesis of this study was that among participants with active RA, MK-8457 100 mg twice daily (BID) was superior to placebo as measured by the change in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) after 12 weeks of treatment. Study was terminated early (12 September 2013) based on preliminary analysis of data. The results of this study need to be interpreted with caution given the small sample size (56 participants) resulting from the early termination of the study.
|
||
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. The following additional measure defined for this individual study was in place for the protection of trial participants. Participants in the base study were eligible for early escape at Week 12 or Week 18, only if they demonstrated a <20% improvement in both tender and swollen joint counts. If participants met the early escape criteria, participants could choose to either withdraw from the study or to continue into the safety extension portion of the study and receive MK-8457 100 mg twice daily (BID) for up to a total of 100 weeks of treatment.
|
||
Background therapy |
Participants were required to be on background methotrexate (MTX) therapy at stable doses prior to and during the base study. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Aug 2012
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
76 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Poland: 8
|
||
Country: Number of subjects enrolled |
Spain: 5
|
||
Country: Number of subjects enrolled |
United Kingdom: 2
|
||
Country: Number of subjects enrolled |
Denmark: 1
|
||
Country: Number of subjects enrolled |
France: 1
|
||
Country: Number of subjects enrolled |
Hungary: 3
|
||
Country: Number of subjects enrolled |
Colombia: 11
|
||
Country: Number of subjects enrolled |
New Zealand: 1
|
||
Country: Number of subjects enrolled |
Korea, Republic of: 6
|
||
Country: Number of subjects enrolled |
United States: 18
|
||
Worldwide total number of subjects |
56
|
||
EEA total number of subjects |
20
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
41
|
||
From 65 to 84 years |
14
|
||
85 years and over |
1
|
|
|||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||
Recruitment details |
This trial was conducted at 53 clinical centers in the United States, Australia, Columbia, Denmark, France, Greece, Hungary, Italy, New Zealand, Poland, South Africa, Spain, and in the United Kingdom. | ||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||
Screening details |
Sixty-four of 120 participants screened for the study were not randomized; 56 were excluded for not meeting at least one of the inclusion or exclusion criteria. Eight participants were being screened but were not randomized due to the early termination of the study. | ||||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||||
Period 1 title |
Base Study
|
||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||
Arm title
|
MK-8457 100mg BID | ||||||||||||||||||||||||
Arm description |
MK-8457 100mg twice daily (BID) for 24 weeks | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
MK-8457
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
MK-8456 100mg, BID, oral daily for 24 weeks
|
||||||||||||||||||||||||
Arm title
|
Placebo | ||||||||||||||||||||||||
Arm description |
Placebo to MK-8457 100mg twice daily (BID) for 24 weeks | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
Placebo to MK-8457 100mg twice daily (BID) for 24 weeks
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [1] - The number of subjects transferring in and out of the arms in the period are not the same. It is expected the net number of transfers in and out of the arms in a period, will be zero. Justification: The number of participants transferring in and out of the arms in the period are not the same as 10 participants had an early escape from the Base Study and transferred into the MK-8457 100 mg BID arm of the Safety Extension Study. |
|||||||||||||||||||||||||
Period 2
|
|||||||||||||||||||||||||
Period 2 title |
Safety Extensions
|
||||||||||||||||||||||||
Is this the baseline period? |
No | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||
Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||
Arm title
|
MK-8457 100 mg | ||||||||||||||||||||||||
Arm description |
MK-8457 (100mg) BID, oral, for up to 76 weeks. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
MK-8457 100mg
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
MK-8456 100mg, BID, oral daily for up to 76 weeks
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [2] - The number of subjects transferring in and out of the arms in the period are not the same. It is expected the net number of transfers in and out of the arms in a period, will be zero. Justification: The number of participants transferring in and out of the arms in the period are not the same as 10 participants had an early escape from the Base Study and transferred into the MK-8457 100 mg BID arm of the Safety Extension Study. |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MK-8457 100mg BID
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
MK-8457 100mg twice daily (BID) for 24 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo to MK-8457 100mg twice daily (BID) for 24 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
MK-8457 100mg BID
|
||
Reporting group description |
MK-8457 100mg twice daily (BID) for 24 weeks | ||
Reporting group title |
Placebo
|
||
Reporting group description |
Placebo to MK-8457 100mg twice daily (BID) for 24 weeks | ||
Reporting group title |
MK-8457 100 mg
|
||
Reporting group description |
MK-8457 (100mg) BID, oral, for up to 76 weeks. |
|
|||||||||||||
End point title |
Change From Baseline in the Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) at Week 12 | ||||||||||||
End point description |
The DAS28-CRP is a continuous parameter derived from the formula: 0.56 × the square root of the tender joint count (0-28) + 0.28 × the square root of the swelling joint count (0-28) + 0.36 × the C reactive protein value (in mg/L +1) + 0.014 × Patient’s Global Assessment of Disease Activity Visual Analog Score of 0-100 mm + 0.96 = a value ranging from 2.0 to 10.0 with higher values meaning higher disease activity. A value of 2.6 was interpreted as remission.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline and Week 12
|
||||||||||||
|
|||||||||||||
Notes [1] - Number of participants with data at both Baseline and Week 12. [2] - Number of participants with data at both baseline and Week 12. |
|||||||||||||
Statistical analysis title |
Treatment Difference | ||||||||||||
Statistical analysis description |
Difference in Least Squares Means between Change from Baseline in DAS-28-CRP for participants taking MK-8457 at Week 12 vs. Change from Baseline in DAS-28-CRP for participants taking placebo at Week 12. Negative differences are in favor of the MK-8457 treatment group in the comparison.
|
||||||||||||
Comparison groups |
Placebo v MK-8457 100mg BID
|
||||||||||||
Number of subjects included in analysis |
31
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [3] | ||||||||||||
P-value |
= 0.308 | ||||||||||||
Method |
Constrained longitudinal data analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.52
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.54 | ||||||||||||
upper limit |
0.5 | ||||||||||||
Notes [3] - Constrained longitudinal data analysis model includes terms for region, screening inflammatory marker level, time in weeks, and treatment by time. A participant needs to have at least one baseline observation or post-baseline observation to be included in the model. |
|
|||||||||||||
End point title |
Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response at Week 12 | ||||||||||||
End point description |
ACR responses are presented as the numerical measurement of improvement in multiple disease assessment criteria. An ACR 20 response is defined as a ≥ 20% improvement in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) (0 = Absent; 1 = Present) and 2. ≥ 20% improvement in 3 of the following 5 assessments: a. A particpant’s overall assessment of pain on a visual analog scale (VAS, 100 mm, no pain to extreme pain); b. Participant’s Global Assessment of Disease Activity (VAS); c. Physician’s Global Assessment of Disease Activity (VAS); d. Patient’s assessment of function as measured by Health Assessment Questionnaire (HAQ). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area.; e. C-Reactive Protein (an inflammatory marker with a normal reference range of less than 0.9 mg/dL).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Notes [4] - Number of participants who completed Week 12 or discontinued before Week 12. [5] - Number of participants who has either completed Week 12 or has discontinued before Week 12. |
|||||||||||||
Statistical analysis title |
Treatment Difference | ||||||||||||
Statistical analysis description |
Percentage of ACR20 responders at Week 12 treated with MK-8457 minus percentage of ACR20 responders at Week 12 treated with placebo.
|
||||||||||||
Comparison groups |
MK-8457 100mg BID v Placebo
|
||||||||||||
Number of subjects included in analysis |
56
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [6] | ||||||||||||
P-value |
= 0.91 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.26
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-23.52 | ||||||||||||
upper limit |
23.01 | ||||||||||||
Notes [6] - Based on Cochran-Mantel-Haenszel test stratified by region and screening inflammatory marker level. |
|
|||||||||||||
End point title |
Percentage of Participants Achieving an ACR20 Response at Week 24 | ||||||||||||
End point description |
Percentage of participants who were ACR20 responders at Week 24. ACR responses were presented as the numerise assessment criteria. An ACR 20 response was defined as a ≥ 20% improvement in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) (0 = Absent; 1 = Present) and 2. ≥ 20% improvement in 3 of the following 5 assessments: a. A particpant’s overall assessment of pain on a visual analog scale (VAS, 100 mm, no pain to extreme pain); b. Participant’s Global Assessment of Disease Activity (VAS); c. Physician’s Global Assessment of Disease Activity (VAS); d. Participant’s assessment of function as measured by Health Assessment Questionnaire (HAQ). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area; e. C-Reactive Protein (an inflammatory marker with a normal reference range of less than 0.9 mg/dL).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Notes [7] - Due to the early termination of the study, this endpoint was not evaluated. [8] - Due to the early termination of the study, this endpoint was not evaluated. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants Achieving ACR50 Response at Week 12 | ||||||||||||
End point description |
Percentage of participants who were ACR50 responders at Week 12. ACR responses are presented as the numerical measurement of improvement in multiple disease assessment criteria. An ACR50 response is defined as a ≥ 50% improvement in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) (0 = Absent; 1 = Present) and 2. ≥ 50% improvement in 3 of the following 5 assessments: a. A participant’s overall assessment of pain on a visual analog scale (VAS, 100 mm, no pain to extreme pain); b. Participant’s Global Assessment of Disease Activity (VAS); c. Physician’s Global Assessment of Disease Activity (VAS); d. Participant’s assessment of function as measured by Health Assessment Questionnaire (HAQ). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area.; e. C-Reactive Protein (an inflammatory marker with a normal reference range of less than 0.9 mg/dL).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Notes [9] - Number of participants who completed Week 12 or discontinued before Week 12. [10] - Number of participants who completed Week 12 or discontinued before Week 12. |
|||||||||||||
Statistical analysis title |
Treatment Difference | ||||||||||||
Statistical analysis description |
Percentage of ACR50 responders at Week 12 treated with MK-8457 minus percentage of ACR50 responders at Week 12 treated with placebo.
|
||||||||||||
Comparison groups |
Placebo v MK-8457 100mg BID
|
||||||||||||
Number of subjects included in analysis |
56
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [11] | ||||||||||||
P-value |
= 0.468 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
8.46
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-10.4 | ||||||||||||
upper limit |
27.32 | ||||||||||||
Notes [11] - Based on Cochran-Mantel-Haenszel test stratified by region and screening inflammatory marker level. |
|
|||||||||||||
End point title |
Change From Baseline in DAS28-CRP at Week 24 | ||||||||||||
End point description |
DAS28 (CRP) is a continuous response validated measure which includes tender and swollen joint count, inflammatory marker, and patient global assessment. The DAS28 based on CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and GH. The DAS28 is a continuous parameter and is defined as follows: DAS28 (CRP) = 0.56 × SQRT(TEN28) + 0.28 × SQRT(SW28) + 0.36 × ln (CRP+1) + 0.014 × GH + 0.96 where: TEN28 is 28 joint count for tenderness; SW28 is 28 joint count for swelling. SQRT is the square root.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 24
|
||||||||||||
|
|||||||||||||
Notes [12] - Due to the early terminaton of the study, this endpoint was not evaluated. [13] - Due to the early terminaton of the study, this endpoint was not evaluated. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in the Health Assessment Questionnaire (HAQ) at Week 12 | ||||||||||||
End point description |
The functional status of the participant was assessed using the Disability Index of the HAQ. This 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 12
|
||||||||||||
|
|||||||||||||
Notes [14] - Number of participants with data at both Baseline and Week 12. [15] - Number of participants with data at both Baseline and Week 12. |
|||||||||||||
Statistical analysis title |
Treatment Difference | ||||||||||||
Statistical analysis description |
Change from baseline in HAQ at Week 12 for participants treated with MK-8457 minus change from baseline in HAQ at Week 12 for participants treated with placebo. Negative differences are in favor of the MK-8457 treatment group in the comparison.
|
||||||||||||
Comparison groups |
MK-8457 100mg BID v Placebo
|
||||||||||||
Number of subjects included in analysis |
31
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [16] | ||||||||||||
P-value |
= 0.038 | ||||||||||||
Method |
Difference in LS Means | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.41
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.79 | ||||||||||||
upper limit |
-0.02 | ||||||||||||
Notes [16] - Constrained longitudinal data analysis model includes terms for region, screening inflammatory marker level, time in weeks, and treatment by time. A participant needed to have at least one baseline observation or post-baseline observation to be included in the model. |
|
|||||||||||||
End point title |
Percentage of Participants Achieving ACR50 Response at Week 24 | ||||||||||||
End point description |
Percentage of participants who were ACR50 responders at Week 24. ACR responses are presented as the numerical measurement of improvement in multiple disease assessment criteria. An ACR50 response is defined as a ≥ 50% improvement in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) (0 = Absent; 1 = Present) and 2. ≥ 50% improvement in 3 of the following 5 assessments: a. A participant’s overall assessment of pain on a visual analog scale (VAS, 100 mm, no pain to extreme pain); b. Participant’s Global Assessment of Disease Activity (VAS); c. Physician’s Global Assessment of Disease Activity (VAS); d. Participant’s assessment of function as measured by Health Assessment Questionnaire (HAQ). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area; e. C-Reactive Protein (an inflammatory marker with a normal reference range of less than 0.9 mg/dL).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Notes [17] - Due to the early termination of the study, this endpoint was not evaluated. [18] - Due to the early termination of the study, this endpoint was not evaluated. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in the HAQ at Week 24 | ||||||||||||
End point description |
The functional status of the participant was assessed using the Disability Index of the HAQ. This 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 24
|
||||||||||||
|
|||||||||||||
Notes [19] - Due to the early terminaton of the study, this endpoint was not evaluated. [20] - Due to the early terminaton of the study, this endpoint was not evaluated. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 102 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MK-8457 100 mg (Base Study)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
MK-8457 100 mg (Safety Extension)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (Base study)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||
Substantial protocol amendments (globally) |
|||||||
Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
21 Aug 2013 |
This amendment was a global amendment and included changes to the primary and secondary objectives, reduction in the sample size, and removal of the second planned interim analysis. No participants were enrolled under this amendment. |
||||||
Interruptions (globally) |
|||||||
Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
The results of this study need to be interpreted with caution given the small sample size (56 participants) resulting from the early termination of the study. |