Clinical Trial to Evaluate the Safety and Efficacy of the Addition of Sitagliptin in Participants With Type 2 Diabetes Mellitus Receiving Acarbose Monotherapy (MK-0431-130)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01177384
First received: June 30, 2010
Last updated: March 10, 2014
Last verified: March 2014
Results First Received: March 10, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Sitagliptin phosphate
Drug: Comparator: Placebo
Drug: Acarbose
Drug: Glimepiride

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All participants randomized population. The participant flow module includes the second sequential randomization of a participant in the placebo group. Data for the second sequential randomization were excluded from the efficacy and safety analyses and the reason for not completed was a protocol violation.

Reporting Groups
  Description
Sitagliptin Sitagliptin 100 mg daily (q.d.) + acarbose (continuing the current stable dose of at least 50 mg three times daily [t.i.d.])
Placebo Placebo q.d. + acarbose (continuing the current stable dose of at least 50 mg t.i.d.)

Participant Flow:   Overall Study
    Sitagliptin     Placebo  
STARTED     191     190 [1]
COMPLETED     177     164  
NOT COMPLETED     14     26  
Adverse Event                 6                 4  
Lack of Efficacy                 0                 1  
Lost to Follow-up                 3                 4  
Physician Decision                 0                 3  
Protocol Violation                 0                 2  
Withdrawal by Subject                 5                 12  
[1] Includes the second randomization of a participant



  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.
All participants randomized population. The baseline characteristics module does not include the second sequential randomization of a participant in the placebo group. Data for the second sequential randomization were excluded from the efficacy and safety analyses.

Reporting Groups
  Description
Sitagliptin Sitagliptin 100 mg daily (q.d.) + acarbose (continuing the current stable dose of at least 50 mg three times daily [t.i.d.])
Placebo Placebo q.d. + acarbose (continuing the current stable dose of at least 50 mg t.i.d.)
Total Total of all reporting groups

Baseline Measures
    Sitagliptin     Placebo     Total  
Number of Participants  
[units: participants]
  191     189     380  
Age  
[units: Years]
Mean ± Standard Deviation
  56.5  ± 8.9     57.8  ± 9.5     57.1  ± 9.2  
Gender  
[units: Participants]
     
Female     94     92     186  
Male     97     97     194  
Hemoglobin A1c (A1C) [1]
[units: Percent]
Mean ± Standard Deviation
  8.09  ± 0.79     8.08  ± 0.90     8.08  ± 0.85  
Fasting plasma glucose  
[units: mg/dL]
Mean ± Standard Deviation
  177.3  ± 37.5     177.5  ± 40.2     177.4  ± 38.8  
[1] Percent of glycosylated hemoglobin



  Outcome Measures
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1.  Primary:   Change From Baseline in Hemoglobin A1c (A1C) at Week 24   [ Time Frame: Baseline and Week 24 ]

Measure Type Primary
Measure Title Change From Baseline in Hemoglobin A1c (A1C) at Week 24
Measure Description A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. Efficacy analyses treated data as missing after the initiation of rescue therapy.
Time Frame Baseline and Week 24  
Safety Issue No  

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.
Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for the A1C subsequent to at least 1 dose of study treatment, or lacked baseline data for the A1C. Last observation carried forward (missing data approach).

Reporting Groups
  Description
Sitagliptin Sitagliptin 100 mg daily (q.d.) + acarbose (continuing the current stable dose of at least 50 mg three times daily [t.i.d.])
Placebo Placebo q.d. + acarbose (continuing the current stable dose of at least 50 mg t.i.d.)

Measured Values
    Sitagliptin     Placebo  
Number of Participants Analyzed  
[units: participants]
  185     180  
Change From Baseline in Hemoglobin A1c (A1C) at Week 24  
[units: Percent]
Least Squares Mean ( 95% Confidence Interval )
  -0.76  
  ( -0.93 to -0.59 )  
  -0.14  
  ( -0.32 to 0.03 )  


Statistical Analysis 1 for Change From Baseline in Hemoglobin A1c (A1C) at Week 24
Groups [1] All groups
Method [2] ANCOVA
P Value [3] <.001
Difference in least squares mean [4] -0.62
95% Confidence Interval ( -0.79 to -0.44 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The ANCOVA model included terms for treatment and prior antihyperglycemic agent (AHA) therapy status (on acarbose monotherapy, or on acarbose in combination with other AHA(s)) and a covariate for baseline A1C.
[4] Other relevant estimation information:
  No text entered.



2.  Primary:   Number of Participants Who Experienced at Least One Adverse Event   [ Time Frame: Up to Week 24 + 14 Day Post-Study Follow-up ]

Measure Type Primary
Measure Title Number of Participants Who Experienced at Least One Adverse Event
Measure Description No text entered.
Time Frame Up to Week 24 + 14 Day Post-Study Follow-up  
Safety Issue Yes  

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.
All participants as treated population defined as all randomized participants who received at least one dose of study drug. Data were excluded after the initiation of rescue therapy.

Reporting Groups
  Description
Sitagliptin Sitagliptin 100 mg daily (q.d.) + acarbose (continuing the current stable dose of at least 50 mg three times daily [t.i.d.])
Placebo Placebo q.d. + acarbose (continuing the current stable dose of at least 50 mg t.i.d.)

Measured Values
    Sitagliptin     Placebo  
Number of Participants Analyzed  
[units: participants]
  191     189  
Number of Participants Who Experienced at Least One Adverse Event  
[units: Participants]
  62     58  

No statistical analysis provided for Number of Participants Who Experienced at Least One Adverse Event



3.  Primary:   Number of Participants Who Discontinued Study Drug Due to an Adverse Event   [ Time Frame: Up to 24 Weeks ]

Measure Type Primary
Measure Title Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Measure Description No text entered.
Time Frame Up to 24 Weeks  
Safety Issue Yes  

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.
All participants as treated population defined as all randomized participants who received at least one dose of study drug. Data were excluded after the initiation of rescue therapy.

Reporting Groups
  Description
Sitagliptin Sitagliptin 100 mg daily (q.d.) + acarbose (continuing the current stable dose of at least 50 mg three times daily [t.i.d.])
Placebo Placebo q.d. + acarbose (continuing the current stable dose of at least 50 mg t.i.d.)

Measured Values
    Sitagliptin     Placebo  
Number of Participants Analyzed  
[units: participants]
  191     189  
Number of Participants Who Discontinued Study Drug Due to an Adverse Event  
[units: Participants]
  5     2  

No statistical analysis provided for Number of Participants Who Discontinued Study Drug Due to an Adverse Event



4.  Secondary:   Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Measure Description Change from baseline at Week 24 is defined as Week 24 FPG minus Week 0 FPG. Efficacy analyses treated data as missing after the initiation of rescue therapy.
Time Frame Baseline and Week 24  
Safety Issue No  

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.
Full Analysis Set, all randomized participants except those who: failed to take at least 1 dose of study treatment, lacked all post-randomization data for the FPG subsequent to at least 1 dose of study treatment, or lacked baseline data for the FPG. Last observation carried forward (missing data approach).

Reporting Groups
  Description
Sitagliptin Sitagliptin 100 mg daily (q.d.) + acarbose (continuing the current stable dose of at least 50 mg three times daily [t.i.d.])
Placebo Placebo q.d. + acarbose (continuing the current stable dose of at least 50 mg t.i.d.)

Measured Values
    Sitagliptin     Placebo  
Number of Participants Analyzed  
[units: participants]
  187     183  
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24  
[units: mg/dL]
Least Squares Mean ( 95% Confidence Interval )
  -17.9  
  ( -25.3 to -10.5 )  
  -3.5  
  ( -11.1 to 4.1 )  


Statistical Analysis 1 for Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Groups [1] All groups
Method [2] ANCOVA
P Value [3] <.001
Difference in least squares mean [4] -14.4
95% Confidence Interval ( -21.8 to -7.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The ANCOVA model included terms for treatment and prior AHA therapy status (on acarbose monotherapy, or on acarbose in combination with other AHA(s)) and a covariate for baseline FPG.
[4] Other relevant estimation information:
  No text entered.




  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
No text entered.


  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


No publications provided


Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01177384     History of Changes
Other Study ID Numbers: 0431-130, 2010_543, CTRI/2011/10/002072
Study First Received: June 30, 2010
Results First Received: March 10, 2014
Last Updated: March 10, 2014
Health Authority: China: Ministry of Health