Clinical Trial Results:
A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Sitagliptin in Pediatric Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control
Summary
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EudraCT number |
2011-002528-42 |
Trial protocol |
LV LT DE ES IT BG AT DK SE HU PL SK Outside EU/EEA GR FR |
Global end of trial date |
09 Oct 2019
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Results information
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Results version number |
v2(current) |
This version publication date |
28 Mar 2021
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First version publication date |
24 Apr 2020
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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
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Trial identification
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Sponsor protocol code |
0431-083
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01485614 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Merck Protocol Number: MK-0431-083 | ||
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) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000470-PIP01-08 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
09 Oct 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Oct 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Oct 2019
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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 purpose of the study was to assess the effect of treatment with sitagliptin compared with placebo on glycated hemoglobin (A1C), and the safety and tolerability of sitagliptin, in pediatric participants (ages 10-17 years) with type 2 diabetes mellitus (T2DM) with inadequate glycemic control. The primary hypothesis for this study was that sitagliptin reduces A1C more than placebo after 20 weeks of treatment. Amendment 5 of the protocol removed 2 arms from the study (Metformin arm and the Placebo followed by Sitagliptin arm). Participants already in these 2 arms continued in the study. EUPASS4468 is a follow-up, observational assessment of safety of participants who participated in the MK-0431-083 study for up to 5 years.
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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 measure defined for this study was in place for the protection of trial participants: glycemic rescue therapy, as appropriate, and as per the study glycemic rescue criteria, consisted of sitagliptin or metformin as an initial glycemic rescue (glycemic Rescue Step 1) and insulin as an additional glycemic rescue (glycemic Rescue Step 2), if needed.
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Background therapy |
Participants who were on insulin at screening continued receiving insulin during the study. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Feb 2012
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
5 Years | ||
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 |
Argentina: 1
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Country: Number of subjects enrolled |
Brazil: 1
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Country: Number of subjects enrolled |
Bulgaria: 6
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Colombia: 3
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Country: Number of subjects enrolled |
Costa Rica: 1
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Country: Number of subjects enrolled |
Dominican Republic: 12
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Country: Number of subjects enrolled |
Guatemala: 14
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Country: Number of subjects enrolled |
Honduras: 3
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Country: Number of subjects enrolled |
Hungary: 6
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Country: Number of subjects enrolled |
Israel: 19
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Country: Number of subjects enrolled |
Italy: 3
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Country: Number of subjects enrolled |
Latvia: 1
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Country: Number of subjects enrolled |
Lithuania: 1
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Country: Number of subjects enrolled |
Malaysia: 13
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Country: Number of subjects enrolled |
Mauritius: 8
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Country: Number of subjects enrolled |
Mexico: 23
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Country: Number of subjects enrolled |
Philippines: 8
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Country: Number of subjects enrolled |
Poland: 2
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Country: Number of subjects enrolled |
Romania: 2
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Country: Number of subjects enrolled |
Russian Federation: 30
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Country: Number of subjects enrolled |
Saudi Arabia: 7
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Country: Number of subjects enrolled |
Serbia: 2
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Country: Number of subjects enrolled |
Thailand: 3
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Country: Number of subjects enrolled |
United Arab Emirates: 2
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Country: Number of subjects enrolled |
United States: 28
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Worldwide total number of subjects |
200
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EEA total number of subjects |
21
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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) |
25
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Adolescents (12-17 years) |
175
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study recruited participants in clinics/clinical offices in 26 countries. | |||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
The Pre-Assignment Period included a one-week single-blind placebo run-in prior to randomization during which participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals. | |||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Randomization
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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, Monitor, Carer | |||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sitagliptin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals. | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Sitagliptin
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Investigational medicinal product code |
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Other name |
MK-0431
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
In this period, participants in the Sitagliptin treatment arm received one tablet of sitagliptin 100 mg prior to the morning meal.
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Investigational medicinal product name |
Placebo matching 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 |
In this period, participants in the Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.
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Arm title
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Placebo/Metformin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals. | |||||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo matching 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 |
In this period, participants in the Placebo/Metformin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.
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Investigational medicinal product name |
Placebo matching Sitagliptin
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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 |
In this period, participants in the Placebo/Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.
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Arm title
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Metformin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, but ongoing participants in this arm continued in the same arm. | |||||||||||||||||||||||||||||||||||
Arm type |
Internal control | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
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 |
In this period, participants in the Metformin treatment arm received two tablets of metformin prior to both the morning and evening meals (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).
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Investigational medicinal product name |
Placebo matching Sitagliptin
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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 |
In this period, participants in the Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.
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Arm title
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Placebo/Sitagliptin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, but ongoing participants in this arm continued in the same arm. | |||||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo matching 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 |
In this period, participants in the Placebo/Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.
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Investigational medicinal product name |
Placebo matching Sitagliptin
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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 |
In this period, participants in the Placebo/Sitagliptin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.
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Period 2
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Period 2 title |
Weeks 0-20
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Is this the baseline period? |
Yes [1] | |||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | |||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sitagliptin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Sitagliptin
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Investigational medicinal product code |
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Other name |
MK-0431
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
In this period, participants in the Sitagliptin treatment arm received one tablet of sitagliptin 100 mg prior to the morning meal.
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Investigational medicinal product name |
Placebo matching 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 |
In this period, participants in the Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.
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Investigational medicinal product name |
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 |
In this period, participants in the Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria received metformin as glycemic Rescue Step 1 (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).
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Investigational medicinal product name |
Insulin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
In this period, participants in the Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.
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Arm title
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Placebo/Metformin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | |||||||||||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo matching Sitagliptin
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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 |
In this period, participants in the Placebo/Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.
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Investigational medicinal product name |
Placebo matching 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 |
In this period, participants in the Placebo/Metformin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.
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Investigational medicinal product name |
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 |
In this period, participants in the Placebo/Metformin treatment arm meeting protocol-specific glycemic rescue criteria received metformin as glycemic Rescue Step 1 (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).
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Investigational medicinal product name |
Insulin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
In this period, participants in the Placebo/Metformin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.
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Arm title
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Metformin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20. | |||||||||||||||||||||||||||||||||||
Arm type |
Internal control | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
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 |
In this period, participants in the Metformin treatment arm received two tablets of metformin prior to both the morning and evening meals (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).
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Investigational medicinal product name |
Placebo matching Sitagliptin
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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 |
In this period, participants in the Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.
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Investigational medicinal product name |
Sitagliptin
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Investigational medicinal product code |
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Other name |
MK-0431
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Metformin treatment arm meeting protocol-specific glycemic rescue criteria received one tablet of sitagliptin 100 mg as glycemic Rescue Step 1.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Metformin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.
|
|||||||||||||||||||||||||||||||||||
Arm title
|
Placebo/Sitagliptin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20. | |||||||||||||||||||||||||||||||||||
Arm type |
Internal control | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo matching Sitagliptin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Sitagliptin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo matching Metformin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Sitagliptin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
MK-0431
|
|||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria received one tablet of sitagliptin 100 mg as glycemic Rescue Step 1.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.
|
|||||||||||||||||||||||||||||||||||
Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: Period 1 is not the baseline period as it displays the all enrolled subject population whereas baseline characteristics are displayed for the all enrolled and treated subject population (Period 2). |
||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||
Notes [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The worldwide number of worldwide subjects enrolled in the study is not the same as the number of subjects reported in the baseline period because the worldwide subjects are the all enrolled subject population whereas baseline period subjects are the all enrolled and treated subject population. |
||||||||||||||||||||||||||||||||||||
Period 3
|
||||||||||||||||||||||||||||||||||||
Period 3 title |
Weeks 20-54
|
|||||||||||||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | |||||||||||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||||||||||
Arm title
|
Sitagliptin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | |||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Sitagliptin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
MK-0431
|
|||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Sitagliptin treatment arm received one tablet of sitagliptin 100 mg prior to the morning meal.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo matching Metformin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Metformin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria received metformin as glycemic Rescue Step 1 (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.
|
|||||||||||||||||||||||||||||||||||
Arm title
|
Placebo/Metformin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | |||||||||||||||||||||||||||||||||||
Arm type |
Comparator | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Metformin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Metformin treatment arm received two tablets of metformin prior to both the morning and evening meals (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo matching Sitagliptin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Sitagliptin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
MK-0431
|
|||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Metformin treatment arm meeting protocol-specific glycemic rescue criteria received one tablet of sitagliptin 100 mg as glycemic Rescue Step 1.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Metformin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.
|
|||||||||||||||||||||||||||||||||||
Arm title
|
Metformin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, but ongoing participants in this arm continued in the same arm during Weeks 20-54. | |||||||||||||||||||||||||||||||||||
Arm type |
Internal control | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Metformin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Metformin treatment arm received two tablets of metformin prior to both the morning and evening meals.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo matching Sitagliptin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Metformin treatment arm received one tablet of placebo matching sitagliptin 100 mg prior to the morning meal.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Sitagliptin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
MK-0431
|
|||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Metformin treatment arm meeting protocol-specific glycemic rescue criteria received one tablet of sitagliptin 100 mg as glycemic Rescue Step 1.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Metformin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.
|
|||||||||||||||||||||||||||||||||||
Arm title
|
Placebo/Sitagliptin | |||||||||||||||||||||||||||||||||||
Arm description |
In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, but ongoing participants in this arm continued in the same arm during Weeks 20-54. | |||||||||||||||||||||||||||||||||||
Arm type |
Comparator | |||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Sitagliptin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
MK-0431
|
|||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Sitagliptin treatment arm received one tablet of sitagliptin 100 mg prior to the morning meal.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo matching Metformin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Sitagliptin treatment arm received two tablets of placebo matching metformin 500 mg prior to both the morning and evening meals.
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Metformin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria received metformin as glycemic Rescue Step 1 (starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily).
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Insulin
|
|||||||||||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||||||||||
Pharmaceutical forms |
Injection
|
|||||||||||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||||||||||
Dosage and administration details |
In this period, participants in the Placebo/Sitagliptin treatment arm meeting protocol-specific glycemic rescue criteria after initiating glycemic Rescue Step 1 continued taking the medication from glycemic Rescue Step 1 and initiated insulin (glycemic Rescue Step 2). Participants on background insulin had their insulin dose increased for glycemic Rescue Step 2.
|
|||||||||||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Sitagliptin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/Metformin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Metformin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/Sitagliptin
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Sitagliptin
|
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.
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Subject analysis set title |
Placebo/Metformin
|
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.
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Subject analysis set title |
Metformin
|
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.
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Subject analysis set title |
Placebo/Sitagliptin
|
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.
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Subject analysis set title |
Placebo (pooled)
|
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
This analysis set, used only for analyses of data during Weeks 0-20, contains the pooled population of placebo-treated participants from the groups "Placebo/Sitagliptin" and "Placebo/Metformin".
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End points reporting groups
|
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Reporting group title |
Sitagliptin
|
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Reporting group description |
In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals. | ||
Reporting group title |
Placebo/Metformin
|
||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals. | ||
Reporting group title |
Metformin
|
||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, but ongoing participants in this arm continued in the same arm. | ||
Reporting group title |
Placebo/Sitagliptin
|
||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, but ongoing participants in this arm continued in the same arm. | ||
Reporting group title |
Sitagliptin
|
||
Reporting group description |
In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | ||
Reporting group title |
Placebo/Metformin
|
||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. | ||
Reporting group title |
Metformin
|
||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20. | ||
Reporting group title |
Placebo/Sitagliptin
|
||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, ongoing participants in this arm continued in the same arm during Weeks 0-20. | ||
Reporting group title |
Sitagliptin
|
||
Reporting group description |
In this period, participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | ||
Reporting group title |
Placebo/Metformin
|
||
Reporting group description |
In this period, participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | ||
Reporting group title |
Metformin
|
||
Reporting group description |
In this period, participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, but ongoing participants in this arm continued in the same arm during Weeks 20-54. | ||
Reporting group title |
Placebo/Sitagliptin
|
||
Reporting group description |
In this period, participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin treatment arm, but ongoing participants in this arm continued in the same arm during Weeks 20-54. | ||
Subject analysis set title |
Sitagliptin
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.
|
||
Subject analysis set title |
Placebo/Metformin
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.
|
||
Subject analysis set title |
Metformin
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.
|
||
Subject analysis set title |
Placebo/Sitagliptin
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The analysis set consisted of all randomized participants in this study arm who received at least 1 dose of study medication and had at least 1 observation for the analysis endpoint.
|
||
Subject analysis set title |
Placebo (pooled)
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
This analysis set, used only for analyses of data during Weeks 0-20, contains the pooled population of placebo-treated participants from the groups "Placebo/Sitagliptin" and "Placebo/Metformin".
|
|
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End point title |
Change from Baseline in Hemoglobin A1C (A1C) at Week 20 [1] | ||||||||||||||||||||
End point description |
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
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End point type |
Primary
|
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End point timeframe |
Baseline and Week 20
|
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned or performed for this primary end point. |
|||||||||||||||||||||
|
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No statistical analyses for this end point |
|
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End point title |
Baseline Glycated Hemoglobin (A1C) for the Placebo (pooled) Arm [2] | ||||||||
End point description |
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes. The analysis population included all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C.
|
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End point type |
Primary
|
||||||||
End point timeframe |
Baseline
|
||||||||
Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned or performed for this primary end point. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline In A1C at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (pooled)) [3] | ||||||||||||
End point description |
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C from a longitudinal data analysis (LDA) model. The placebo arm in this comparison is a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The Statistical Analysis Plan (SAP) did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
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End point type |
Primary
|
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End point timeframe |
Baseline and Week 20
|
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Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This end point is displaying data and statistical analyses for only selected arms of the study. Data and statistical analyses for other arms in the baseline period are presented in other end points. |
|||||||||||||
|
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Statistical analysis title |
Difference in Change from Baseline | ||||||||||||
Statistical analysis description |
The Least Squares (LS) Mean for the arm "Sitagliptin" is compared against that of "Placebo (pooled)".
|
||||||||||||
Comparison groups |
Sitagliptin v Placebo (pooled)
|
||||||||||||
Number of subjects included in analysis |
190
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.448 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Least Squares Means Difference | ||||||||||||
Point estimate |
-0.19
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.68 | ||||||||||||
upper limit |
0.3 |
|
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End point title |
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 [4] | |||||||||||||||
End point description |
The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The analysis population includes all randomized participants who received ≥1 dose of study medication.
|
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End point type |
Primary
|
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End point timeframe |
Up to Week 56
|
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned or performed for this primary end point. |
||||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
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End point title |
Percentage of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) | ||||||||||||
End point description |
The number of participants experiencing ≥1 adverse event during Weeks 0-56 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. The analysis population includes all randomized participants who received ≥1 dose of study medication. Participants (n=5) from the Placebo/Sitagliptin arm were excluded because sitagliptin received during Week 0-54 was an inappropriate control for the Sitagliptin arm which received sitagliptin during both study treatment phases.
|
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End point type |
Primary
|
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End point timeframe |
Up to Week 56
|
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|
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Statistical analysis title |
Difference in Percentage | ||||||||||||
Statistical analysis description |
The percentage of participants who experienced ≥1 adverse event for the arm "Sitagliptin" is compared against that of "Placebo/Metformin". Analysis based on the Miettinen & Nurminen method.
|
||||||||||||
Comparison groups |
Sitagliptin v Placebo/Metformin
|
||||||||||||
Number of subjects included in analysis |
185
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in Percentage | ||||||||||||
Point estimate |
2.4
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-10 | ||||||||||||
upper limit |
14.9 |
|
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End point title |
Number of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 [5] | |||||||||||||||
End point description |
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The analysis population includes all randomized participants who received ≥1 dose of study medication.
|
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End point type |
Primary
|
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End point timeframe |
Up to Week 54
|
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned or performed for this primary end point. |
||||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During Weeks 0-54 (Analysis of Selected Arms: Sitagliptin and Placebo/Metformin) | ||||||||||||
End point description |
The percentage of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. The analysis population includes all randomized participants who received ≥1 dose of study medication. Participants (n=5) from the Placebo/Sitagliptin arm were excluded because sitagliptin received during Week 0-54 was an inappropriate control for the Sitagliptin arm which received sitagliptin during both study treatment phases.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to Week 54
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in percentage | ||||||||||||
Statistical analysis description |
The percentage of participants who experienced ≥1 adverse event for the arm "Sitagliptin" is compared against that of "Placebo/Metformin". Analysis based on the Miettinen & Nurminen method.
|
||||||||||||
Comparison groups |
Sitagliptin v Placebo/Metformin
|
||||||||||||
Number of subjects included in analysis |
185
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
4.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.3 | ||||||||||||
upper limit |
10.8 |
|
|||||||||||||||||||||
End point title |
Change from Baseline in A1C at Week 54 | ||||||||||||||||||||
End point description |
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. This change from baseline reflects the Week 54 A1C minus the Week 0 A1C. The analysis population included all randomized participants who took at least one dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [6] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
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No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants With A1C at Goal (<7.0%) at Week 20 | ||||||||||||||||||||
End point description |
The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. All numbers shown in each individual treatment group are based on the observed values (Missing = Not at Goal). The analysis population included all randomized participants who received ≥1 dose of study medication.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With A1C at Goal (<7.0%) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (pooled)) [7] | ||||||||||||
End point description |
The percentage of participants with A1C at goal (<7.0%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The placebo arm in this comparison is a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. The analysis population included all randomized participants who received ≥1 dose of study medication.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 20
|
||||||||||||
Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This end point is displaying data and statistical analyses for only selected arms of the study. Data and statistical analyses for other arms in the baseline period are presented in other end points. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in Percentage | ||||||||||||
Statistical analysis description |
The percentage of participants with an A1C at the A1C goal (7.0%) in the arm "Sitagliptin" was compared against the arm "Placebo (pooled)". For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method based on the LDA model was used to impute whether the participant had met the goal.
|
||||||||||||
Comparison groups |
Sitagliptin v Placebo (pooled)
|
||||||||||||
Number of subjects included in analysis |
190
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.374 | ||||||||||||
Method |
Miettinen and Nurminen | ||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
6.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-8.1 | ||||||||||||
upper limit |
21.2 |
|
|||||||||||||||||||||
End point title |
Percentage of Participants With A1C at Goal (<6.5%) at Week 20 | ||||||||||||||||||||
End point description |
The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. All numbers shown in each individual treatment group are based on the observed values (Missing = Not at Goal). The analysis population included all randomized participants who received ≥1 dose of study medication.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With A1C at Goal (<6.5) at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (pooled)) [8] | ||||||||||||
End point description |
The percentage of participants with A1C at goal (<6.5%) at Week 20 was presented. The analysis table includes the observed values for each treatment arm (Missing = Not at Goal) and the estimated treatment difference (Missing = Multiple Imputation). The current outcome measure focused on comparing results from participants randomized to sitagliptin or placebo. The placebo arm in this comparison is a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. The analysis population included all randomized participants who received ≥1 dose of study medication.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 20
|
||||||||||||
Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This end point is displaying data and statistical analyses for only selected arms of the study. Data and statistical analyses for other arms in the baseline period are presented in other end points. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in Percentage | ||||||||||||
Statistical analysis description |
The percentage of participants with an A1C at the A1C goal (6.5%) in the arm "Sitagliptin" was compared against the arm "Placebo (pooled)". For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method based on the LDA model was used to impute whether the participant had met the goal. model.
|
||||||||||||
Comparison groups |
Sitagliptin v Placebo (pooled)
|
||||||||||||
Number of subjects included in analysis |
190
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.639 | ||||||||||||
Method |
Miettinen and Nurminen | ||||||||||||
Parameter type |
Difference in percentage | ||||||||||||
Point estimate |
3.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-11.6 | ||||||||||||
upper limit |
18.3 |
|
|||||||||||||||||||||
End point title |
Percentage of Participants With A1C at Goal (<7.0%) at Week 54 | ||||||||||||||||||||
End point description |
The percentage of participants with A1C at goal (<7.0%) at Week 54 was presented. All numbers shown in each individual treatment group are based on the observed values (Missing = Not at Goal). The analysis population included all randomized participants who received ≥1 dose of study medication.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants With A1C at Goal (<6.5%) at Week 54 | ||||||||||||||||||||
End point description |
The percentage of participants with A1C at goal (<6.5%) at Week 54 was presented. All numbers shown in each individual treatment group are based on the observed values (Missing = Not at Goal). The analysis population included all randomized participants who received ≥1 dose of study medication.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Fasting Plasma Glucose (FPG) at Week 20 | ||||||||||||||||||||
End point description |
Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Baseline Fasting Plasma Glucose (FPG) for the Placebo (pooled) Arm | ||||||||
End point description |
Blood glucose was measured on a fasting basis. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at baseline.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Baseline
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change from Baseline in FPG at Week 20 (Analysis of Selected Arms: Sitagliptin and Placebo (pooled)) [9] | ||||||||||||
End point description |
Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 20 minus FPG at baseline and was estimated from a longitudinal data analysis model. The current outcome measure focused on results from participants randomized to sitagliptin or placebo. The placebo arm in this comparison is a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately. The analysis population includes all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||
Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This end point is displaying data and statistical analyses for only selected arms of the study. Data and statistical analyses for other arms in the baseline period are presented in other end points. |
|||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in Change from Baseline | ||||||||||||
Statistical analysis description |
The Least Squares (LS) Mean for the arm "Sitagliptin" was compared against that of "Placebo (pooled)".
|
||||||||||||
Comparison groups |
Sitagliptin v Placebo (pooled)
|
||||||||||||
Number of subjects included in analysis |
190
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.849 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Least Squares Means Difference | ||||||||||||
Point estimate |
1.5
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-14.4 | ||||||||||||
upper limit |
17.5 |
|
|||||||||||||||||||||
End point title |
Change from Baseline in FPG at Week 54 | ||||||||||||||||||||
End point description |
Blood glucose was measured on a fasting basis. Change in plasma glucose levels was FPG at Week 54 minus FPG at baseline. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [10] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in 2-Hour Post-meal Glucose (PMG) at Week 20 | ||||||||||||||||||||
End point description |
PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour PMG minus the Week 0 2-hour PMG. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in 2-hour PMG at Week 54 | ||||||||||||||||||||
End point description |
PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour PMG minus the Week 0 2-hour PMG. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [11] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in 2-hour Incremental PMG at Week 20 | ||||||||||||||||||||
End point description |
2-Hour incremental PMG = Glucose at 120 minutes – glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 2-hour incremental PMG minus the Week 0 2-hour incremental PMG. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in 2-Hour Incremental PMG at Week 54 | ||||||||||||||||||||
End point description |
2-Hour incremental PMG = Glucose at 120 minutes – glucose at 0 minutes. PMG endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 2-hour incremental PMG minus the Week 0 2-hour incremental PMG. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint both at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [12] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin at Week 20 for Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
This change from baseline reflects the Week 20 insulin minus the Week 0 insulin. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin at Week 54 For Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
This change from baseline reflects the Week 54 insulin minus the Week 0 insulin. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [13] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Proinsulin at Week 20 For Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
This change from baseline reflects the Week 20 proinsulin minus the Week 0 proinsulin. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Proinsulin at Week 54 For Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
This change from baseline reflects the Week 54 proinsulin minus the Week 0 proinsulin. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [14] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Proinsulin/Insulin Ratio at Week 20 for Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
Change from baseline was the Week 20 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Proinsulin/Insulin Ratio at Week 54 For Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
The change from baseline was Week 54 proinsulin/insulin ratio minus the Week 0 proinsulin/insulin ratio. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [15] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Homeostatic Model Assessment of β-cell Function (HOMA-β) at Week 20 For Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] – 3.5}. The change from baseline was Week 20 HOMA-β minus the Week 0 HOMA-β. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in HOMA-β at Week 54 For Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
HOMA-β = 20 × fasting insulin (in mcIU/mL) ÷ {[FPG (in mg/dL)/18] – 3.5}. This change from baseline was Week 54 HOMA-β minus the Week 0 HOMA-β. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [16] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 20 For Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 20 HOMA-IR minus the Week 0 HOMA-IR. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in HOMA-IR at Week 54 For Participants Not on Background Insulin | ||||||||||||||||||||
End point description |
HOMA-IR = fasting insulin (in mcIU/mL) × FPG (in mg/dL) / (22.5×18). This change from baseline was Week 54 HOMA-IR minus the Week 0 HOMA-IR. The analysis population included all randomized participants not on background insulin who received ≥1 dose of study medication and had data for the analysis endpoint both at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [17] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Glucose 3-Hour Total Area Under the Curve (AUC) at Week 20 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin 3-hour AUC at Week 20 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in C-peptide 3-Hour AUC at Week 20 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin 3-Hour AUC/ Glucose 3-Hour AUC Ratio at Week 20 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 20 insulin total AUC/glucose total AUC ratio minus the Week 0 insulin total AUC/glucose total AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Glucose Excursion 3-Hour AUC at Week 20 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at Baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin Excursion 3-Hour AUC at Week 20 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in C-peptide Excursion 3-Hour AUC at Week 20 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 20 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 20 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Glucose 3-Hour AUC at Week 54 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 glucose 3-hour AUC minus the Week 0 glucose 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [18] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin 3-Hour AUC at Week 54 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC minus the Week 0 insulin 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [19] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in C-peptide 3-Hour AUC at Week 54 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 C-peptide 3-hour AUC minus the Week 0 C-peptide 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [20] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin 3-Hour AUC/Glucose 3-Hour AUC Ratio at Week 54 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. This change from baseline was Week 54 insulin 3-hour AUC/glucose 3-hour AUC ratio minus the Week 0 insulin 3-hour AUC/glucose 3-hour AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [21] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Glucose Excursion 3-Hour AUC at Week 54 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 glucose Excursion 3-hour AUC minus the Week 0 glucose Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [22] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin Excursion 3-Hour AUC at Week 54 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC minus the Week 0 insulin Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [23] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in C-Peptide Excursion 3-Hour AUC at Week 54 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 C-peptide Excursion 3-hour AUC minus the Week 0 C-peptide Excursion 3-hour AUC. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [24] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Insulin Excursion 3-Hour AUC/Glucose Excursion 3-Hour AUC Ratio at Week 54 | ||||||||||||||||||||
End point description |
AUC endpoints were derived via the trapezoidal rule using 9-point Meal Tolerance Test (MTT) measurements. Excursion AUC = Incremental AUC above the level at the start of the meal. AUC below the level at the start of the meal did not contribute to the Excursion AUC. This change from baseline was Week 54 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio minus the Week 0 insulin Excursion 3-hour AUC/glucose Excursion 3-hour AUC ratio. The analysis population included all randomized participants who received ≥1 dose of study medication, consented to participate in the MTT, and had data for the analysis endpoint at baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54 (-10 min. before ingesting the meal, 0 min. prior to the meal, 10, 20, 30, 60, 90, 120, 180 minutes after ingesting the meal)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [25] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | ||||||||||||||||||||
End point description |
The percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported. The analysis population included all randomized participants who received ≥1 dose of study medication.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Up to Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 54 | ||||||||||||||||||||
End point description |
The percentage of participants who initiated glycemic rescue therapy prior to Week 54 was reported. The analysis population included all randomized participants who received ≥1 dose of study medication.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Up to Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Body Mass Index (BMI) at Week 20 | ||||||||||||||||||||
End point description |
This change from baseline was Week 20 BMI minus the Week 0 BMI. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in BMI at Week 54 | ||||||||||||||||||||
End point description |
This change from baseline was Week 54 BMI minus the Week 0 BMI. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Mean Percent Change from Baseline in Blood Mononuclear Cells Expressing CD26 at Week 20 | ||||||||||||||||||||
End point description |
The percent change from baseline in CD26 = ([CD26 value at Week 20] - [baseline CD26 value] ÷ baseline CD26 value) × 100. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Mean Percent Change from Baseline in Peripheral Blood Mononuclear Cells Expressing CD26 at Week 54 | ||||||||||||||||||||
End point description |
The percent change from baseline in CD26 = ([CD26 value at Week 54] - [baseline CD26 value] ÷ baseline CD26 value) × 100. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
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 Calcitonin at Week 20 - Females | ||||||||||||||||||||
End point description |
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Calcitonin at Week 54 - Females | ||||||||||||||||||||
End point description |
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
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 Calcitonin at Week 20 - Males | ||||||||||||||||||||
End point description |
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 20 calcitonin minus the Week 0 calcitonin. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Calcitonin at Week 54 - Males | ||||||||||||||||||||
End point description |
Calcitonin, along with parathyroid hormone, is a hormone that regulates calcium and bone metabolism. This change from baseline was Week 54 calcitonin minus the Week 0 calcitonin. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [26] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Urine N-terminal Cross-linking Telopeptide of Bone Collagen [u-NTx]/Creatinine Ratio at Week 20 - Females | ||||||||||||||||||||
End point description |
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20. BCE = Bone Collagen Equivalents
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline u-NTx/Creatinine Ratio at Week 20 - Males | ||||||||||||||||||||
End point description |
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [27] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in u-NTx/Creatinine Ratio at Week 54 - Females | ||||||||||||||||||||
End point description |
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
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 u-NTx/Creatinine Ratio at Week 54 - Males | ||||||||||||||||||||
End point description |
Urine N-terminal cross-linking telopeptide of bone collagen [u-NTx]/creatinine ratio is a biochemical marker of bone turnover/resorption. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. All participants in the Metformin arm were missing baseline or Week 54 measurements.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [28] - All participants in this arm were missing baseline or Week 54 measurements. [29] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 20 - Females | ||||||||||||||||||||
End point description |
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Females | ||||||||||||||||||||
End point description |
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
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 Bone-Specific Alkaline Phosphatase at Week 20 - Males | ||||||||||||||||||||
End point description |
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 20 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Bone-Specific Alkaline Phosphatase at Week 54 - Males | ||||||||||||||||||||
End point description |
Bone-specific alkaline phosphatase is a biochemical marker of bone turnover. This change from baseline was Week 54 bone-specific alkaline phosphatase minus the Week 0 bone-specific alkaline phosphatase. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [30] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percent Change from Baseline in Insulin-like Growth Factor-1 (IGF-1) at Week 20 - Females | ||||||||||||||||||||
End point description |
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value] ÷ baseline IGF-1 value) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percent Change from Baseline in IGF-1 at Week 54 - Females | ||||||||||||||||||||
End point description |
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value] ÷ baseline IGF-1 value) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [31] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percent Change from Baseline in IGF-1 at Week 20 - Males | ||||||||||||||||||||
End point description |
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 20] - [baseline IGF-1 value] ÷ baseline IGF-1 value) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percent Change from Baseline in IGF-1 at Week 54 - Males | ||||||||||||||||||||
End point description |
IGF-1 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-1 = ([IGF-1 value at Week 54] - [baseline IGF-1 value] ÷ baseline IGF-1 value) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [32] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percent Change from Baseline in Insulin-like Growth Factor Binding Protein 3 (IGF-BP3) at Week 20 - Females | ||||||||||||||||||||
End point description |
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value] ÷ baseline IGF-BP3 value) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
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|
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No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percent Change from Baseline in IGF-BP3 at Week 54 - Females | ||||||||||||||||||||
End point description |
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value] ÷ baseline IGF-BP3 value) × 100. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percent Change from Baseline in IGF-BP3 at Week 20 - Males | ||||||||||||||||||||
End point description |
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 20] - [baseline IGF-BP3 value] ÷ baseline IGF-BP3 value) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percent Change from Baseline in IGF-BP3 at Week 54 - Males | ||||||||||||||||||||
End point description |
IGF-BP3 is a biochemical marker of growth hormone action and growth. The percent change from baseline in IGF-BP3 = ([IGF-BP3 value at Week 54] - [baseline IGF-BP3 value] ÷ baseline IGF-BP3 value) × 100. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
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Notes [33] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
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No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Growth Velocity at Week 20 - Females | ||||||||||||||||||||
End point description |
Growth Velocity = change from baseline in height/change from baseline in chronologic age. The analysis population included all female randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 20
|
||||||||||||||||||||
|
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No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Growth Velocity at Week 54 - Females | ||||||||||||||||||||
End point description |
Growth Velocity = change from baseline in height/change from baseline in chronologic age. The analysis population included all female randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Growth Velocity at Week 20 - Males | ||||||||||||||||||||
End point description |
Growth Velocity = change from baseline in height/change from baseline in chronologic age. The analysis population included all male randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 20
|
||||||||||||||||||||
|
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No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Growth Velocity at Week 54 - Males | ||||||||||||||||||||
End point description |
Growth Velocity = change from baseline in height/change from baseline in chronologic age. The analysis population included all male randomized participants who received ≥1 dose of study medication and had height data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [34] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Skeletal Maturation at Week 20 - Females | ||||||||||||||||||||
End point description |
Skeletal Maturation = change from baseline in bone age/change from baseline in chronologic age. Bone age was determined from an X-ray of left hand and wrist. The analysis population included all female randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Skeletal Maturation at Week 54 - Females | ||||||||||||||||||||
End point description |
Skeletal Maturation = change from baseline in bone age/change from baseline in chronologic age. Bone age was determined from X-ray of left hand and wrist. The analysis population included all female randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 54. All participants in the Placebo/Sitagliptin arm were missing baseline or Week 54 measurements.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [35] - All participants in this arm were missing baseline or Week 54 measurements. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Skeletal Maturation at Week 20 - Males | ||||||||||||||||||||
End point description |
Skeletal Maturation = change from baseline in bone age/change from baseline in chronologic age. Bone age was determined from X-ray of left hand and wrist. The analysis population included all male randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [36] - "9999" The standard deviation could not be calculated because only one participant was analyzed. [37] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Skeletal Maturation at Week 54 - Males | ||||||||||||||||||||
End point description |
Skeletal Maturation = change from baseline in bone age/change from baseline in chronologic age. Bone age was determined from X-ray of left hand and wrist. The analysis population included all male randomized participants who received ≥1 dose of study medication and had bone age data for the analysis endpoint at both baseline and Week 54. All participants in the Metformin and Placebo/Sitagliptin arms were missing baseline or Week 54 measurements.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [38] - All participants in this arm were missing baseline or Week 54 measurements. [39] - All participants in this arm were missing baseline or Week 54 measurements. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Tanner Staging for Genitalia at Week 20 - Males | ||||||||||||||||||||
End point description |
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 20 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [40] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Tanner Staging for Genitalia at Week 54 - Males | ||||||||||||||||||||
End point description |
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of genital development (males) with a score of range 1 to 5 where 1=no development and 5=adult genitals. This change from baseline was Week 54 Tanner Staging for Genitalia minus the Week 0 Tanner Staging for Genitalia. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. All participants in the Metformin arm were missing baseline or Week 54 measurements.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [41] - All participants in this arm were missing baseline or Week 54 measurements. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Tanner Staging for Breasts at Week 20 - Females | ||||||||||||||||||||
End point description |
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 20 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Tanner Staging for Breasts at Week 54 - Females | ||||||||||||||||||||
End point description |
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of breast development (females). Tanner stage (breast) is a score of range 1 to 5 where 1=no development and 5=adult breast. This change from baseline was Week 54 Tanner Staging for Breasts minus the Week 0 Tanner Staging for Breasts. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
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 Tanner Stage for Public Hair at Week 20 - Females | ||||||||||||||||||||
End point description |
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development. Tanner stage (pubic hair) is a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Tanner Stage for Pubic Hair at Week 54 - Females | ||||||||||||||||||||
End point description |
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in female participants. Tanner staging includes an assessment of pubic hair development with a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. The analysis population included all female randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54.
|
||||||||||||||||||||
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 Tanner Stage for Public Hair at Week 20 - Males | ||||||||||||||||||||
End point description |
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development with a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 20 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 20.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 20
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [42] - "9999" The standard deviation could not be calculated because only one participant was analyzed. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Change from Baseline in Tanner Stage for Pubic Hair at Week 54 - Males | ||||||||||||||||||||
End point description |
Participant's stage of sexual maturation was assessed using the Tanner staging measure for determining pubertal development in male participants. Tanner staging includes an assessment of pubic hair development with a score of range 1 to 5 where 1=no development and 5=adult pubic hair. This change from baseline was Week 54 Tanner Staging for Pubic Hair minus the Week 0 Tanner Staging for Pubic Hair. The analysis population included all male randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at both baseline and Week 54. Tanner staging results for pubic hair were unavailable for the Metformin arm.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and Week 54
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [43] - All participants in this arm were missing baseline or Week 54 measurements. |
|||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Worsening in Dental Status at Week 20 | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening included participants with worsening of tooth fracture, tooth discoloration, or enamel defect as determined by the independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 20 dental assessments versus Baseline dental assessments. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at Week 20.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 20
|
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|
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No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants with Worsening in Dental Status at Week 54 | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
Participants were evaluated with a visual oral exam; a subset had dental photographs. Teeth worsening included participants with worsening of tooth fracture, tooth discoloration, or enamel defect as determined by the independent reviewer. Worsening in these categories was a change in dental defect assessments made by comparing Week 20 dental assessments versus Baseline dental assessments. The analysis population included all randomized participants who received ≥1 dose of study medication and had data for the analysis endpoint at Week 54.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 54
|
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No statistical analyses for this end point |
|
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Adverse events information
|
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Timeframe for reporting adverse events |
SAEs and AEs: Up to approximately Week 56. Deaths: Up to approximately 42 months after randomization.
|
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Adverse event reporting additional description |
The All-Cause Mortality analysis population consisted of all randomized participants. The AE analysis population consisted of all participants who received >=1 dose of study medication and included all post-randomization follow-ups. One participant in the Sitagliptin arm died after the study treatment phases, about 42 months after randomization.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.1
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Reporting groups
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Reporting group title |
Sitagliptin
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Reporting group description |
Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/Metformin
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Reporting group description |
Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Metformin
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Reporting group description |
Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants continued to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Metformin treatment arm, but ongoing participants in this arm continued in this arm during Weeks 0-54. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/Sitagliptin
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Reporting group description |
Participants received 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants received 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. Amendment 5 of the protocol ended enrollment in the Placebo/Sitagliptin arm, but ongoing participants in this arm continued in this arm during Weeks 0-54. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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27 May 2013 |
AM1 - Global amendment. Procedural and administrative changes. |
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25 Feb 2014 |
AM5 - Global amendment: Lengthened the Phase A placebo-controlled portion from 16 weeks to 20 weeks. Modified visit schedule to reduce the total number of visits from 13 to 11. Removed the metformin group and the placebo/sitagliptin group from the study. Based on revised power calculations, the sample size for the entire study was reduced from 360 participants to 170 participants – 2 treatment groups (sitagliptin or placebo) with 85 participants/group. Changed inclusion criterion of A1C from ≥7% to ≥6.5%. Modified the timeframe for prior treatment with insulin from 6 months to 12 weeks. |
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12 Feb 2015 |
AM7 - Global amendment. Included participants on background insulin. |
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01 Dec 2015 |
AM9 - Global amendment. Changed “adverse experience” to “adverse event.” Complied with recommendations from the US FDA to minimize missing data. |
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03 Feb 2017 |
AM12 - Global amendment. Added the dental substudy. |
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18 Jul 2018 |
AM16 - Global amendment. Complied with the recommendations from a health authority. Increased sample size. Clarified statistical methods for analyses using the Treatment Effect estimand. Added analyses using the Treatment Policy estimand. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |