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A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266)

This study has been terminated.
(Merck terminated the study for business reasons in November 2013.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01678820
First received: August 31, 2012
Last updated: October 16, 2014
Last verified: October 2014
Results First Received: October 16, 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/Simvastatin FDC
Drug: Sitagliptin
Drug: Simvastatin
Drug: Placebo to sitagliptin
Drug: Placebo to simvastatin
Drug: Placebo to Sitagliptin/Simvastatin FDC
Drug: Metformin
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.

Reporting Groups
  Description
Sitagliptin/Simvastatin FDC Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Sitagliptin Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Simvastatin Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

Participant Flow:   Overall Study
    Sitagliptin/Simvastatin FDC     Sitagliptin     Simvastatin  
STARTED     100     99     100  
Treated With Double-blind Study Drug     100     97     98  
COMPLETED     38     36     43  
NOT COMPLETED     62     63     57  
Study Terminated by Sponsor                 45                 43                 43  
Withdrawal by Subject                 2                 5                 2  
Protocol Specified Criteria                 2                 3                 1  
Adverse Event                 2                 2                 2  
Lost to Follow-up                 7                 2                 2  
Non-compliance with study drug                 0                 1                 0  
Physician Decision                 0                 0                 1  
Protocol Violation                 4                 5                 4  
Not treated with double-blind study drug                 0                 2                 2  



  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. Study specific baseline characteristics include all randomized participants with data.

Reporting Groups
  Description
Sitagliptin/Simvastatin FDC Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Sitagliptin Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Simvastatin Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Total Total of all reporting groups

Baseline Measures
    Sitagliptin/Simvastatin FDC     Sitagliptin     Simvastatin     Total  
Number of Participants  
[units: participants]
  100     99     100     299  
Age  
[units: Years]
Mean ± Standard Deviation
  54.9  ± 10.2     54.2  ± 10.3     54.9  ± 10.0     54.7  ± 10.1  
Gender  
[units: Participants]
       
Female     45     52     49     146  
Male     55     47     51     153  
Hemoglobin A1c (A1C)  
[units: Percent]
Mean ± Standard Deviation
  8.16  ± 0.94     8.15  ± 1.09     8.22  ± 1.19     8.18  ± 1.08  
Fasting plasma glucose (FPG)  
[units: mg/dL]
Mean ± Standard Deviation
  169.9  ± 42.3     175.9  ± 48.6     175.7  ± 49.3     173.8  ± 46.8  
Low-density lipoprotein cholesterol (LDL-C)  
[units: mg/dL]
Mean ± Standard Deviation
  106.5  ± 26.7     103.9  ± 24.2     100.9  ± 22.0     103.7  ± 24.4  
Total cholesterol (TC)  
[units: mg/dL]
Mean ± Standard Deviation
  189.3  ± 30.9     187.7  ± 29.6     183.5  ± 28.4     186.8  ± 29.6  
Apolipoprotein B (Apo B) [1]
[units: mg/dL]
Mean ± Standard Deviation
  97.8  ± 19.0     95.4  ± 19.0     94.1  ± 17.2     95.8  ± 18.4  
Non high-density lipoprotein cholesterol (non-HDL-C) [2]
[units: mg/dL]
Mean ± Standard Deviation
  141.7  ± 30.9     139.5  ± 29.9     136.5  ± 27.1     139.2  ± 29.3  
Triglycerides (TG)  
[units: mg/dL]
Mean ± Standard Deviation
  177.4  ± 101.2     180.8  ± 119.1     184.2  ± 118.6     180.8  ± 112.9  
High-density lipoprotein cholesterol (HDL-C)  
[units: mg/dL]
Mean ± Standard Deviation
  47.6  ± 11.3     48.2  ± 12.1     47.0  ± 11.2     47.6  ± 11.5  
Very low-density lipoprotein cholesterol (VLDL-C) [2]
[units: mg/dL]
Mean ± Standard Deviation
  35.4  ± 18.8     35.8  ± 20.4     35.7  ± 18.8     35.6  ± 19.3  
[1] Sitagliptin, n=95; Total, n=295
[2] Sitagliptin, n=97; Total, n=297



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)   [ Time Frame: Baseline and Week 16 ]

2.  Primary:   Number of Participants Who Experienced at Least One Adverse Event (AE)   [ Time Frame: Up to 16 weeks for non-serious AEs, up to 18 weeks for serious AEs ]

3.  Primary:   Number of Participants Who Discontinued Study Drug Due to an Adverse Event   [ Time Frame: Up to 16 weeks ]

4.  Secondary:   Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)   [ Time Frame: Baseline and Week 16 ]

5.  Secondary:   Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16   [ Time Frame: Baseline and Week 16 ]

6.  Secondary:   Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16   [ Time Frame: Baseline and Week 16 ]

7.  Secondary:   Percent Change From Baseline in Total Cholesterol (TC) at Week 16   [ Time Frame: Baseline and Week 16 ]

8.  Secondary:   Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16   [ Time Frame: Baseline and Week 16 ]

9.  Secondary:   Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16   [ Time Frame: Baseline and Week 16 ]

10.  Secondary:   Percent Change From Baseline in Triglycerides (TG) at Week 16   [ Time Frame: Baseline and Week 16 ]

11.  Secondary:   Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 16   [ Time Frame: Baseline and Week 16 ]

12.  Secondary:   Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16   [ Time Frame: Baseline and Week 16 ]

13.  Secondary:   Percentage of Participants With A1C Level <7% at Week 16   [ Time Frame: Week 16 ]


  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
Study was terminated for business reasons in November 2013.


  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: NCT01678820     History of Changes
Other Study ID Numbers: 0431D-266
Study First Received: August 31, 2012
Results First Received: October 16, 2014
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration