Clinical Trial Results:
A Multicenter, Phase III, Randomized, Placebo-Controlled Trial to Assess the Safety and Efficacy of MK-3102 Monotherapy in Subjects with Type 2 Diabetes Mellitus and Inadequate Glycemic Control
Summary
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EudraCT number |
2012-003626-24 |
Trial protocol |
HU DE NL IT BG |
Global end of trial date |
19 Jun 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jun 2016
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First version publication date |
26 Jun 2016
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Other versions |
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 |
3102-011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01717313 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Protocol number: MK-3102-011 | ||
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 |
19 Jun 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Jun 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Jun 2015
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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 |
The main objectives of this study were to assess the effect of treatment with omarigliptin (MK-3102) compared with placebo on hemoglobin A1C (A1C) after 24 weeks and to assess the safety and tolerability of omarigliptin. The primary hypothesis of this study is that after 24 weeks, treatment with omarigliptin compared with placebo provides greater reduction in A1C.
Care must be taken in the interpretation of the results in this study as the non-protocol-specific prohibited use of metformin among a number of participants may have impacted the safety and efficacy results disproportionally among study groups.
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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.
The following additional measures defined for this individual study were in place for the protection of trial subjects. In Phase A, glycemic rescue was with open-label metformin. In Phase B, glycemic rescue was with open-label glimepiride; if glimepiride was not available in the country of the investigator site, another locally available sulfonylurea (SU) was used.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Dec 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Bulgaria: 10
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Country: Number of subjects enrolled |
Germany: 36
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Country: Number of subjects enrolled |
Hungary: 44
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Country: Number of subjects enrolled |
Italy: 13
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Country: Number of subjects enrolled |
Netherlands: 17
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Country: Number of subjects enrolled |
Philippines: 36
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Country: Number of subjects enrolled |
Romania: 49
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Country: Number of subjects enrolled |
Korea, Republic of: 12
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Country: Number of subjects enrolled |
Taiwan: 40
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Country: Number of subjects enrolled |
United States: 72
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Worldwide total number of subjects |
329
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EEA total number of subjects |
169
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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) |
255
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From 65 to 84 years |
74
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants had Type 2 diabetes mellitus (T2DM) and must be >=18 years of age (for India >=18 and <=65 years of age) on the day of signing the informed consent form. | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
The double-blind treatment period included a 24-week placebo-controlled (omarigliptin/omarigliptin-matching placebo) period (Phase A) and a 30-week active-controlled period with blinded metformin/metformin matching placebo (Phase B). | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Phase A (Weeks 0 to 24)
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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 | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Omarigliptin | |||||||||||||||||||||||||||
Arm description |
Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally once a week plus placebo to metformin daily (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Omarigliptin
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
MK-3102
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Omarigliptin 25 mg, oral, once a week for 54 weeks
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Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
If necessary, participants may have glycemic rescue therapy initiated with open-label metformin in Phase A. Participants in the placebo treatment group who were not rescued with open-label metformin will be switched to blinded metformin (starting at 500 mg b.i.d with up-titration to 1000 mg b.i.d) in a blinded manner in Phase B. Subjects who were previously rescued with open-label metformin in Phase A will continue in the trial on open-label metformin.
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Investigational medicinal product name |
Placebo to metformin
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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 |
During Phase B of the study, participants in the omarigliptin treatment group who did not initiate glycemic rescue therapy during Phase A will receive placebo to metformin for 30 weeks (Phase B of the study).
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Investigational medicinal product name |
Glimepiride
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Investigational medicinal product code |
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Other name |
Armaryl®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy.
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Arm title
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Placebo to Omarigliptin | |||||||||||||||||||||||||||
Arm description |
Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin daily for an additional 30 weeks (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B. | |||||||||||||||||||||||||||
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 |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo to omarigliptin, oral, for 54 weeks.
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Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
If necessary, participants may have glycemic rescue therapy initiated with open-label metformin. Participants in the placebo treatment group who were not rescued with open-label metformin will be switched to blinded metformin (starting at 500 mg b.i.d with up-titration to 1000 mg b.i.d) in a blinded manner. Subjects who were previously rescued with open-label metformin in Phase A will continue in the trial on open-label metformin.
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Investigational medicinal product name |
Glimepiride
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Armaryl®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy.
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Period 2
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Period 2 title |
Interphase
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Is this the baseline period? |
No | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Omarigliptin | |||||||||||||||||||||||||||
Arm description |
Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally plus placebo to metformin (Phase B). Open-label metformin may be initiated as glycemic rescue therapy during Phase A. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Omarigliptin
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
MK-3102
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Omarigliptin 25 mg, oral, once a week for 54 weeks
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Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
If necessary, participants may have glycemic rescue therapy initiated with open-label metformin in Phase A. Participants in the placebo treatment group who were not rescued with open-label metformin will be switched to blinded metformin (starting at 500 mg b.i.d with up-titration to 1000 mg b.i.d) in a blinded manner in Phase B. Subjects who were previously rescued with open-label metformin in Phase A will continue in the trial on open-label metformin.
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Investigational medicinal product name |
Placebo to metformin
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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 |
During Phase B of the study, participants in the omarigliptin treatment group who did not initiate glycemic rescue therapy during Phase A will receive placebo to metformin for 30 weeks (Phase B of the study).
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Investigational medicinal product name |
Glimepiride
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Armaryl®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy.
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Arm title
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Placebo to Omarigliptin | |||||||||||||||||||||||||||
Arm description |
Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin for an additional 30 weeks (Phase B). Open-label metformin may be initiated as glycemic rescue therapy during Phase A. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | |||||||||||||||||||||||||||
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 |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo to omarigliptin, oral, for 54 weeks.
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Investigational medicinal product name |
Glimepiride
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|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Armaryl®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy.
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Investigational medicinal product name |
Metformin
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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|||||||||||||||||||||||||||
Dosage and administration details |
If necessary, participants may have glycemic rescue therapy initiated with open-label metformin. Participants in the placebo treatment group who were not rescued with open-label metformin will be switched to blinded metformin (starting at 500 mg b.i.d with up-titration to 1000 mg b.i.d) in a blinded manner. Subjects who were previously rescued with open-label metformin in Phase A will continue in the trial on open-label metformin.
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Period 3
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Period 3 title |
Phase B (Weeks 24 to 54)
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Is this the baseline period? |
No | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Omarigliptin | |||||||||||||||||||||||||||
Arm description |
Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally plus placebo to metformin (Phase B). Open-label metformin may be initiated as glycemic rescue therapy during Phase A. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Omarigliptin
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
MK-3102
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Pharmaceutical forms |
Capsule
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|||||||||||||||||||||||||||
Routes of administration |
Oral use
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|||||||||||||||||||||||||||
Dosage and administration details |
Omarigliptin 25 mg, oral, once a week for 54 weeks
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|||||||||||||||||||||||||||
Investigational medicinal product name |
Metformin
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|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
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|||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
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|||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||
Dosage and administration details |
If necessary, participants may have glycemic rescue therapy initiated with open-label metformin in Phase A. Participants in the placebo treatment group who were not rescued with open-label metformin will be switched to blinded metformin (starting at 500 mg b.i.d with up-titration to 1000 mg b.i.d) in a blinded manner in Phase B. Subjects who were previously rescued with open-label metformin in Phase A will continue in the trial on open-label metformin.
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Investigational medicinal product name |
Placebo to metformin
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
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|||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||
Dosage and administration details |
During Phase B of the study, participants in the omarigliptin treatment group who did not initiate glycemic rescue therapy during Phase A will receive placebo to metformin for 30 weeks (Phase B of the study).
|
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Investigational medicinal product name |
Glimepiride
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Armaryl®
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||
Dosage and administration details |
If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy.
|
|||||||||||||||||||||||||||
Arm title
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Placebo to Omarigliptin | |||||||||||||||||||||||||||
Arm description |
Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin for an additional 30 weeks (Phase B). Open-label metformin may be initiated as glycemic rescue therapy during Phase A. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Capsule
|
|||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Placebo to omarigliptin, oral, for 54 weeks.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Glimepiride
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Armaryl®
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||
Dosage and administration details |
If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Metformin
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||
Dosage and administration details |
If necessary, participants may have glycemic rescue therapy initiated with open-label metformin. Participants in the placebo treatment group who were not rescued with open-label metformin will be switched to blinded metformin (starting at 500 mg b.i.d with up-titration to 1000 mg b.i.d) in a blinded manner. Subjects who were previously rescued with open-label metformin in Phase A will continue in the trial on open-label metformin.
|
|||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Omarigliptin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally once a week plus placebo to metformin daily (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo to Omarigliptin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin daily for an additional 30 weeks (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Omarigliptin
|
||
Reporting group description |
Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally once a week plus placebo to metformin daily (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B. | ||
Reporting group title |
Placebo to Omarigliptin
|
||
Reporting group description |
Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin daily for an additional 30 weeks (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B. | ||
Reporting group title |
Omarigliptin
|
||
Reporting group description |
Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally plus placebo to metformin (Phase B). Open-label metformin may be initiated as glycemic rescue therapy during Phase A. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | ||
Reporting group title |
Placebo to Omarigliptin
|
||
Reporting group description |
Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin for an additional 30 weeks (Phase B). Open-label metformin may be initiated as glycemic rescue therapy during Phase A. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | ||
Reporting group title |
Omarigliptin
|
||
Reporting group description |
Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally plus placebo to metformin (Phase B). Open-label metformin may be initiated as glycemic rescue therapy during Phase A. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | ||
Reporting group title |
Placebo to Omarigliptin
|
||
Reporting group description |
Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin for an additional 30 weeks (Phase B). Open-label metformin may be initiated as glycemic rescue therapy during Phase A. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | ||
Subject analysis set title |
Omarigliptin - Overall Study (Phase A+B) - FAS Population
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The Full Analysis Set (FAS) comprised of all participants who received at least one dose of trial therapy and have a baseline measurement or a post-randomization measurement.
|
||
Subject analysis set title |
Placebo to Omar. - Overall Study (Phase A+B) - FAS Pop.
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The FAS comprised of all participants who received at least one dose of trial therapy and have a baseline measurement or a post-randomization measurement.
|
||
Subject analysis set title |
Omarigliptin - Overall Study (Phase A+B) - Safety Pop.
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The APaT population included all participants who received at least one dose of study drug.
|
||
Subject analysis set title |
Placebo to Omar. - Overall Study (Phase A+B) - Safety Pop.
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The APaT population included all participants who received at least one dose of study drug.
|
||
Subject analysis set title |
Omarigliptin - Overall Study (Phase A+B) - Per-Protocol Pop.
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The Per-Protocol population excluded participants from the FAS population who either had <75% drug compliance or used a prohibited medication (including metformin).
|
||
Subject analysis set title |
PBO to Omar. - Overall Study (Phase A+B) - Per-Protocol Pop.
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The Per-Protocol population excluded participants from the FAS population who either had <75% drug compliance or used a prohibited medication (including metformin).
|
|
|||||||||||||
End point title |
Change from baseline in hemoglobin A1c (A1C) at Week 24 (Phase A, FAS Population) | ||||||||||||
End point description |
The Full Analysis Set (FAS) population was all participants who received at least 1 dose of study treatment and have a baseline measurement for the analysis endpoint and a post-randomization measurement for the analysis endpoint after at least 1 dose of study treatment.
Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline and Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||
Statistical analysis description |
Constrained Longitudinal Data Analysis included terms for treatment, time, prior antihyperglycemic agent (AHA) therapy status, interaction of time by treatment, and time by prior AHA therapy status
|
||||||||||||
Comparison groups |
Omarigliptin v Placebo to Omarigliptin
|
||||||||||||
Number of subjects included in analysis |
329
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||
Parameter type |
Difference in the least squares means | ||||||||||||
Point estimate |
-0.39
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.59 | ||||||||||||
upper limit |
-0.19 |
|
|||||||||||||
End point title |
Percentage of participants who experienced at least one adverse event in Phase A (excluding data after glycemic rescue, Safety Population) | ||||||||||||
End point description |
An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. The All-Participants-as-Treated (APaT) population included all participants who received at least one dose of study drug.
This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 27 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Differences in Percentages | ||||||||||||
Comparison groups |
Omarigliptin v Placebo to Omarigliptin
|
||||||||||||
Number of subjects included in analysis |
329
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
Miettinen & Nurminen method | ||||||||||||
Parameter type |
Differences in percentages | ||||||||||||
Point estimate |
-8.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-18.8 | ||||||||||||
upper limit |
2.6 |
|
|||||||||||||
End point title |
Percentage of participants who discontinued from the study drug due to an adverse event in Phase A (excluding data after glycemic rescue, Safety Population) | ||||||||||||
End point description |
An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. The APaT population included all participants who received at least one dose of study drug.
This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 24 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in Percentages | ||||||||||||
Comparison groups |
Omarigliptin v Placebo to Omarigliptin
|
||||||||||||
Number of subjects included in analysis |
329
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
Miettinen & Nurminen method | ||||||||||||
Parameter type |
Difference in percentages | ||||||||||||
Point estimate |
0.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.1 | ||||||||||||
upper limit |
4.5 |
|
|||||||||||||
End point title |
Percentage of participants who experienced at least one adverse event (Phase A + Phase B, excluding data after glycemic rescue, Safety Population) | ||||||||||||
End point description |
An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. The APaT population included all participants who received at least one dose of study drug.
This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 57 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in percentages vs. placebo | ||||||||||||
Comparison groups |
Omarigliptin - Overall Study (Phase A+B) - Safety Pop. v Placebo to Omar. - Overall Study (Phase A+B) - Safety Pop.
|
||||||||||||
Number of subjects included in analysis |
329
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentages vs. placebo | ||||||||||||
Point estimate |
-5.8
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-16.4 | ||||||||||||
upper limit |
4.9 |
|
|||||||||||||
End point title |
Percentage of participants who discontinued from the study drug due to an adverse event (Phase A + Phase B, excluding data after glycemic rescue, Safety Population) | ||||||||||||
End point description |
An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. The APaT population included all participants who received at least one dose of study drug.
This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 54 weeks
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in percentages vs. placebo | ||||||||||||
Comparison groups |
Omarigliptin - Overall Study (Phase A+B) - Safety Pop. v Placebo to Omar. - Overall Study (Phase A+B) - Safety Pop.
|
||||||||||||
Number of subjects included in analysis |
329
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentages vs. placebo | ||||||||||||
Point estimate |
0.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-3.5 | ||||||||||||
upper limit |
4.8 |
|
|||||||||||||
End point title |
Change from baseline in hemoglobin A1c (A1C) at Week 24 (Phase A, Per-Protocol population) | ||||||||||||
End point description |
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Thus, this change from baseline reflects the Week 24 A1C minus the Week 0 A1C. The Per-Protocol population excluded participants from the FAS population who either had <75% drug compliance or used a prohibited medication (including metformin). A post-hoc sensitivity analysis was performed that excluded participants in both treatment groups who were found to have used prohibited metformin (see results above for a description of the use of prohibited metformin).
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Baseline and Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||
Statistical analysis description |
Constrained Longitudinal Data Analysis included terms for treatment, time, prior antihyperglycemic agent (AHA) therapy status, interaction of time by treatment, and time by prior AHA therapy status
|
||||||||||||
Comparison groups |
Omarigliptin - Overall Study (Phase A+B) - Per-Protocol Pop. v PBO to Omar. - Overall Study (Phase A+B) - Per-Protocol Pop.
|
||||||||||||
Number of subjects included in analysis |
280
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||
Parameter type |
Difference in the least squares means | ||||||||||||
Point estimate |
-0.53
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.75 | ||||||||||||
upper limit |
-0.32 |
|
|||||||||||||
End point title |
Change from baseline in fasting plasma glucose (FPG) at Week 24 (Phase A, FAS Population) | ||||||||||||
End point description |
The FAS population received at least 1 dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint after at least 1 dose of study treatment.
Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||
Statistical analysis description |
Constrained Longitudinal Data Analysis included terms for treatment, time, prior AHA therapy status, the interaction of time by treatment, and time by prior AHA therapy status
|
||||||||||||
Comparison groups |
Omarigliptin v Placebo to Omarigliptin
|
||||||||||||
Number of subjects included in analysis |
329
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.036 | ||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||
Parameter type |
Difference in the least squares means | ||||||||||||
Point estimate |
-10.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-19.9 | ||||||||||||
upper limit |
-0.7 |
|
|||||||||||||
End point title |
Percentage of participants who achieve an A1C goal of <7% (53 mmol/mol) at Week 24 (Phase A, FAS Population) | ||||||||||||
End point description |
The FAS population received at least 1 dose of study treatment and had a baseline measurement for the analysis endpoint and a post-randomization measurement for the analysis endpoint after at least 1 dose of study treatment, and estimated using standard multiple imputation techniques.
Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group Rate Difference | ||||||||||||
Comparison groups |
Omarigliptin v Placebo to Omarigliptin
|
||||||||||||
Number of subjects included in analysis |
329
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Miettinen & Nurminen method | ||||||||||||
Parameter type |
Between-group rate difference | ||||||||||||
Point estimate |
20.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
10.5 | ||||||||||||
upper limit |
29.8 |
|
|||||||||||||
End point title |
Percentage of participants who achieve an A1C goal of <7% at Week 54 (Phase A + Phase B, FAS Population) | ||||||||||||
End point description |
The FAS population was comprised of all participants who received at least 1 dose of study treatment and have a baseline measurement or a post-randomization measurement for the analysis endpoint after at least 1 dose of study treatment.
The results of the study at Week 54 may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 54
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in 2-hour post meal glucose (PMG) at Week 24 (Phase A, FAS Population) | ||||||||||||
End point description |
The FAS population was comprised of all participants who received at least 1 dose of study treatment and have a baseline measurement or a post-randomization measurement for the analysis endpoint after at least 1 dose of study treatment.
Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||
Statistical analysis description |
Constrained Longitudinal Data Analysis included terms for treatment, time, prior AHA therapy status, the interaction of time by treatment, and time by prior AHA therapy status
|
||||||||||||
Comparison groups |
Omarigliptin v Placebo to Omarigliptin
|
||||||||||||
Number of subjects included in analysis |
208
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.177 | ||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||
Parameter type |
Difference in the least squares means | ||||||||||||
Point estimate |
-11.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-28.6 | ||||||||||||
upper limit |
5.3 |
|
|||||||||||||
End point title |
Change from baseline in A1C at Week 54 (Phase A + Phase B, FAS Population) | ||||||||||||
End point description |
A1C (%) reports average blood glucose levels over prolonged periods of time. The FAS population received at least 1 dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint after at least 1 dose of study treatment.
The results of the study at Week 54 may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from baseline in FPG at Week 54 (Phase A + Phase B, FAS Population) | ||||||||||||
End point description |
Blood glucose was measured on a fasting basis (FPG Week 54 - Week 0). The FAS population received at least 1 dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint after at least 1 dose of study treatment.
The results of the study at Week 54 may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of participants who achieve an A1C goal of <6.5% (48 mmol/mol) at Week 24 (Phase A, FAS Population) | ||||||||||||
End point description |
A1C (%) reports average blood glucose levels over prolonged periods of time. The FAS population received at least 1 dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint after at least 1 dose of study treatment. Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Between-group Rate Difference | ||||||||||||
Comparison groups |
Omarigliptin v Placebo to Omarigliptin
|
||||||||||||
Number of subjects included in analysis |
329
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.001 | ||||||||||||
Method |
Miettinen & Nurminen method | ||||||||||||
Parameter type |
Between-group rate difference | ||||||||||||
Point estimate |
11.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
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lower limit |
4.8 | ||||||||||||
upper limit |
18.6 |
|
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End point title |
Percentage of participants who achieve an A1C goal of <6.5% at Week 54 (Phase A + Phase B, FAS Population) | ||||||||||||
End point description |
A1C (%) reports average blood glucose levels over prolonged periods of time. The FAS population received at least 1 dose of study treatment and had a baseline measurement or a post-randomization measurement for the analysis endpoint after at least 1 dose of study treatment.
The results of the study at Week 54 may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).
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End point type |
Secondary
|
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End point timeframe |
Week 54
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No statistical analyses for this end point |
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End point title |
Change from baseline in FPG at Week 24 (Phase A, Per-Protocol population) | ||||||||||||
End point description |
Blood glucose was measured on a fasting basis (collected after a 10-hour fast). FPG is expressed as mg/dL. This change from baseline reflects the FPG level at Week 24 minus the FPG level at Week 0. The Per-Protocol population excluded participants from the FAS population who either had <75% drug compliance or used a prohibited medication (including metformin).A post-hoc sensitivity analysis was performed that excluded participants in both treatment groups who were found to have used prohibited metformin (see results above for a description of the use of prohibited metformin).
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End point type |
Secondary
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End point timeframe |
Baseline and Week 24
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Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||
Statistical analysis description |
Constrained Longitudinal Data Analysis included terms for treatment, time, prior AHA therapy status, the interaction of time by treatment, and time by prior AHA therapy status
|
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Comparison groups |
Omarigliptin v Placebo to Omarigliptin
|
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Number of subjects included in analysis |
280
|
||||||||||||
Analysis specification |
Post-hoc
|
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Analysis type |
other | ||||||||||||
P-value |
= 0.014 | ||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||
Parameter type |
Difference in the least squares means | ||||||||||||
Point estimate |
-13.2
|
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-23.7 | ||||||||||||
upper limit |
-2.7 |
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End point title |
Change from baseline in 2-hour PMG at Week 24 (Phase A, Per-Protocol Population) | ||||||||||||
End point description |
Blood glucose was measured 2 hours after a meal (2-hour PMG). 2-hour PMG is expressed as mg/dL. This change from baseline in 2-Hour PMG reflects the Week 24 2-hour PMG minus the Week 0 2-hour PMG. The Per Protocol population excluded participants from the FAS population who either had <75% drug compliance or used a prohibited medication (including metformin).
A post-hoc sensitivity analysis was performed that excluded participants in both treatment groups who were found to have used prohibited metformin (see results above for a description of the use of prohibited metformin).
|
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End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 24
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in the Least Squares Means | ||||||||||||
Statistical analysis description |
Constrained Longitudinal Data Analysis included terms for treatment, time, prior AHA therapy status, the interaction of time by treatment, and time by prior AHA therapy status
|
||||||||||||
Comparison groups |
Omarigliptin v Placebo to Omarigliptin
|
||||||||||||
Number of subjects included in analysis |
175
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
other | ||||||||||||
P-value |
= 0.031 | ||||||||||||
Method |
Constrained Longitudinal Data Analysis | ||||||||||||
Parameter type |
Difference in the least squares means | ||||||||||||
Point estimate |
-20.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-39 | ||||||||||||
upper limit |
-1.9 |
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Adverse events information
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Timeframe for reporting adverse events |
Up to 57 weeks for serious adverse events (SAE, including 3-week follow-up) and up to 54 weeks for non-serious adverse events.
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Adverse event reporting additional description |
SAE tables include data after glycemic rescue. Non-serious adverse event tables exclude data after glycemic rescue.
This analysis may have been confounded by use of prohibited metformin (see use of prohibited metformin).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Omarigliptin
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Reporting group description |
Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally plus placebo to metformin (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo to Omarigliptin
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Reporting group description |
Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin for an additional 30 weeks (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride may be initiated as glycemic rescue therapy during Phase B. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
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Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
01 Feb 2013 |
AM1 - Added an upper age limit of 65 years to the inclusion criteria for participants enrolled in India; added use of sodium-glucose cotransporter (SGLT2) inhibitor within12 weeks prior to signing informed consent to the exclusion criteria; added that participants who could not tolerate the minimum dose of metformin should be discontinued; added that participants with pancreatitis should be discontinued; and clarified that in specific circumstances, participants should be discontinued from blinded study medication (not the trial) |
||
05 Apr 2013 |
AM2 - added use of omarigliptin at any time prior to signing informed consent to the exclusion criteria; added a 6 month timeframe to the weight loss medication exclusion; included weight loss medications under prohibited medications; and added amylase and lipase to the chemistry panel at the request of regulatory authorities in the European Union |
||
18 Feb 2014 |
AM3 - reduced the sample size from 200 participants per treatment group (400 total participants) to 150 participants per treatment group (300 total participants). |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Care must be taken in the interpretation of the results in this study as the non-protocol-specific prohibited use of metformin among a significant number of participants may have impacted the safety and efficacy results. |