A Study of the Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose When Added to Sitagliptin + Metformin Combination Therapy in Chinese Participants With Diabetes (MK-0431-313)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01709305
First received: October 16, 2012
Last updated: April 6, 2016
Last verified: April 2016
Results First Received: April 6, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Metformin
Drug: Sitagliptin
Drug: Acarbose
Drug: Repaglinide
Drug: Glimepiride
Drug: Gliclazide

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Adult Chinese participants (≥18 and ≤75 years of age) with a diagnosis of Type 2 Diabetes Mellitus (T2DM) and inadequate glycemic control were selected to participate in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
There were 2344 participants who achieved A1C<7% in Phase 1; they completed Phase 1 and did not enter Phase 2. Of the remaining 2589 participants, 377 participants did not meet randomization criteria to enter Phase 2.

Reporting Groups
  Description
Phase 1: Sitagliptin + Metformin During Phase 1, participants received sitagliptin 100 mg + metformin (Week 0 through Week 20). There were 5570 participants enrolled in Phase 1.
Phase 2: Metformin + Sitagliptin + Glimepiride During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 552 participants randomized to this arm in Phase 2.
Phase 2: Metformin + Sitagliptin + Repaglinide During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 550 participants randomized to this arm in Phase 2.
Phase 2: Metformin + Sitagliptin + Acarbose During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 556 participants randomized to this arm in Phase 2.
Phase 2: Metformin + Sitagliptin + Gliclazide During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combinatino therapy for 24 weeks (Week 20 through Week 44). There were 554 participants randomized to this arm in Phase 2.

Participant Flow for 2 periods

Period 1:   Phase 1
    Phase 1: Sitagliptin + Metformin     Phase 2: Metformin + Sitagliptin + Glimepiride     Phase 2: Metformin + Sitagliptin + Repaglinide     Phase 2: Metformin + Sitagliptin + Acarbose     Phase 2: Metformin + Sitagliptin + Gliclazide  
STARTED     5570     0     0     0     0  
COMPLETED     4933     0     0     0     0  
NOT COMPLETED     637     0     0     0     0  
Clinical Adverse Event                 80                 0                 0                 0                 0  
Death                 2                 0                 0                 0                 0  
Hyperglycemia (lack of efficacy)                 13                 0                 0                 0                 0  
Laboratory Adverse Event                 16                 0                 0                 0                 0  
Lost to Follow-up                 147                 0                 0                 0                 0  
Travel, moving, etc.                 30                 0                 0                 0                 0  
Physician Decision                 13                 0                 0                 0                 0  
Protocol Violation                 118                 0                 0                 0                 0  
Withdrawal by Subject                 218                 0                 0                 0                 0  

Period 2:   Phase 2
    Phase 1: Sitagliptin + Metformin     Phase 2: Metformin + Sitagliptin + Glimepiride     Phase 2: Metformin + Sitagliptin + Repaglinide     Phase 2: Metformin + Sitagliptin + Acarbose     Phase 2: Metformin + Sitagliptin + Gliclazide  
STARTED     0     552     550     556     554  
COMPLETED     0     500     505     508     507  
NOT COMPLETED     0     52     45     48     47  
Clinical Adverse Event                 0                 10                 10                 6                 11  
Death                 0                 0                 1                 0                 0  
Hyperglycemia (lack of efficacy)                 0                 0                 0                 0                 2  
Laboratory Adverse Event                 0                 1                 0                 1                 1  
Lost to Follow-up                 0                 10                 6                 9                 5  
Travel, moving, etc.                 0                 2                 3                 3                 5  
Physician Decision                 0                 2                 0                 1                 2  
Protocol Violation                 0                 19                 19                 13                 9  
Withdrawal by Subject                 0                 8                 6                 15                 12  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This population includes all participants who enrolled in Phase 1 and were GCP compliant.

Reporting Groups
  Description
Overall Study During Phase 1, participants received sitagliptin 100 mg + metformin (Week 0 through Week 20).

Baseline Measures
    Overall Study  
Number of Participants  
[units: participants]
  5535  
Age  
[units: Years]
Mean (Standard Deviation)
  53.1  (9.9)  
Gender  
[units: Participants]
 
Female     2240  
Male     3295  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Phase 2 Baseline to Week 44 in Hemoglobin A1c (HbA1c) Levels (Phase 2)   [ Time Frame: Phase 2 Baseline (Week 20) and Week 44 ]

2.  Secondary:   Change From Phase 2 Baseline to Week 44 in Participant Body Weight (Phase 2)   [ Time Frame: Phase 2 Baseline (Week 20), Week 44 ]

3.  Secondary:   Percentage of Participants With Hypoglycemia Events (Phase 2)   [ Time Frame: From Week 20 through Week 44 ]

4.  Secondary:   Percentage of Participants With a Gastrointestinal (GI) AE of Nausea (Phase 2)   [ Time Frame: From Week 20 through Week 44 ]

5.  Secondary:   Percentage of Participants With a GI AE of Vomiting (Phase 2)   [ Time Frame: From Week 20 through Week 44 ]

6.  Secondary:   Percentage of Participants With a GI AE of Diarrhea (Phase 2)   [ Time Frame: From Week 20 through Week 44 ]

7.  Secondary:   Percentage of Participants With a GI AE of Abdominal Pain (Phase 2)   [ Time Frame: From Week 20 through Week 44 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com



Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01709305     History of Changes
Other Study ID Numbers: 0431-313
Study First Received: October 16, 2012
Results First Received: April 6, 2016
Last Updated: April 6, 2016
Health Authority: China: Ministry of Health