Effects of Glimepiride on Recovery From Hypoglycemia in Participants With Type 2 Diabetes Mellitus (MK-0000-253)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01614769
First received: June 6, 2012
Last updated: July 1, 2014
Last verified: July 2014
Results First Received: January 2, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: Placebo
Drug: Glimepiride 2 mg
Drug: Glimepiride 4 mg
Procedure: Hypoglycemic Clamp

  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
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Placebo → Glimepiride 2 mg → Glimepiride 4 mg Participants received placebo in the first period, 2 mg glimepiride in the second period and 4 mg glimepiride in the third period, with a 7-day washout between each period.
Glimepiride 2 mg → Glimepiride 4 mg → Placebo Participants received 2 mg glimepiride in the first period, 4 mg glimepiride in the second period and placebo in the third period, with a 7-day washout between each period.
Glimepiride 4 mg → Placebo → Glimepiride 2 mg Participants received 4 mg glimepiride in the first period, placebo in the second period and 2 mg glimepiride in the third period, with a 7-day washout between each period.
Placebo → Glimepiride 4 mg → Glimepiride 2 mg Participants received placebo in the first period, 4 mg glimepiride in the second period and 2 mg glimepiride in the third period, with a 7-day washout between each period.
Glimepiride 2 mg → Placebo → Glimepiride 4 mg Participants received 2 mg glimepiride in the first period, placebo in the second period and 4 mg glimepiride in the third period, with a 7-day washout between each period.
Glimepiride 4 mg → Glimepiride 2 mg → Placebo Participants received 4 mg glimepiride in the first period, 2 mg glimepiride in the second period and placebo in the third period, with a 7-day washout between each period.

Participant Flow for 5 periods

Period 1:   Period 1
    Placebo → Glimepiride 2 mg → Glimepiride 4 mg     Glimepiride 2 mg → Glimepiride 4 mg → Placebo     Glimepiride 4 mg → Placebo → Glimepiride 2 mg     Placebo → Glimepiride 4 mg → Glimepiride 2 mg     Glimepiride 2 mg → Placebo → Glimepiride 4 mg     Glimepiride 4 mg → Glimepiride 2 mg → Placebo  
STARTED     2     1     2     2     1     2  
COMPLETED     1     1     2     0     1     1  
NOT COMPLETED     1     0     0     2     0     1  
Discontinued due to Hypoglycemia                 0                 0                 0                 1                 0                 1  
Protocol Violation                 0                 0                 0                 1                 0                 0  
Withdrawal by Subject                 1                 0                 0                 0                 0                 0  

Period 2:   7-Day Washout
    Placebo → Glimepiride 2 mg → Glimepiride 4 mg     Glimepiride 2 mg → Glimepiride 4 mg → Placebo     Glimepiride 4 mg → Placebo → Glimepiride 2 mg     Placebo → Glimepiride 4 mg → Glimepiride 2 mg     Glimepiride 2 mg → Placebo → Glimepiride 4 mg     Glimepiride 4 mg → Glimepiride 2 mg → Placebo  
STARTED     1     1     2     0     1     1  
COMPLETED     1     1     2     0     1     1  
NOT COMPLETED     0     0     0     0     0     0  

Period 3:   Period 2
    Placebo → Glimepiride 2 mg → Glimepiride 4 mg     Glimepiride 2 mg → Glimepiride 4 mg → Placebo     Glimepiride 4 mg → Placebo → Glimepiride 2 mg     Placebo → Glimepiride 4 mg → Glimepiride 2 mg     Glimepiride 2 mg → Placebo → Glimepiride 4 mg     Glimepiride 4 mg → Glimepiride 2 mg → Placebo  
STARTED     1     1     2     0     1     1  
COMPLETED     1     1     2     0     1     1  
NOT COMPLETED     0     0     0     0     0     0  

Period 4:   7-Day Washout
    Placebo → Glimepiride 2 mg → Glimepiride 4 mg     Glimepiride 2 mg → Glimepiride 4 mg → Placebo     Glimepiride 4 mg → Placebo → Glimepiride 2 mg     Placebo → Glimepiride 4 mg → Glimepiride 2 mg     Glimepiride 2 mg → Placebo → Glimepiride 4 mg     Glimepiride 4 mg → Glimepiride 2 mg → Placebo  
STARTED     1     1     2     0     1     1  
COMPLETED     1     1     2     0     1     1  
NOT COMPLETED     0     0     0     0     0     0  

Period 5:   Period 3
    Placebo → Glimepiride 2 mg → Glimepiride 4 mg     Glimepiride 2 mg → Glimepiride 4 mg → Placebo     Glimepiride 4 mg → Placebo → Glimepiride 2 mg     Placebo → Glimepiride 4 mg → Glimepiride 2 mg     Glimepiride 2 mg → Placebo → Glimepiride 4 mg     Glimepiride 4 mg → Glimepiride 2 mg → Placebo  
STARTED     1     1     2     0     1     1  
COMPLETED     1     1     1     0     1     1  
NOT COMPLETED     0     0     1     0     0     0  
Withdrawal by Subject                 0                 0                 1                 0                 0                 0  



  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.
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Reporting Groups
  Description
All Participants All randomized participants

Baseline Measures
    All Participants  
Number of Participants  
[units: participants]
  10  
Age  
[units: Years]
Mean ± Standard Deviation
  49.3  ± 5.5  
Gender  
[units: Participants]
 
Female     4  
Male     6  



  Outcome Measures
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1.  Primary:   Recovery Time From Hypoglycemia to Euglycemia   [ Time Frame: From 1 to 180 minutes post hypoglycemic clamp ]
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Measure Type Primary
Measure Title Recovery Time From Hypoglycemia to Euglycemia
Measure Description Immediately after release of the hypoglycemic clamp, which maintained blood glucose close to 50 mg/dL, the time taken until glucose reached euglycemia, defined as 3 consecutive measurements >= 70 mg/dL, is called the recovery time.
Time Frame From 1 to 180 minutes post hypoglycemic clamp  
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.
The per-protocol population consisting of participants who received drug and completed the necessary post treatment measurements for at least one treatment period.

Reporting Groups
  Description
Placebo Participants received placebo in a treatment period.
Glimepiride 2 mg Participants received 2 mg Glimepiride in a treatment period.
Glimepiride 4 mg Participants received 4 mg Glimepiride in a treatment period.

Measured Values
    Placebo     Glimepiride 2 mg     Glimepiride 4 mg  
Number of Participants Analyzed  
[units: participants]
  6     5     6  
Recovery Time From Hypoglycemia to Euglycemia  
[units: Minutes]
Least Squares Mean ( 90% Confidence Interval )
  74.49  
  ( 48.20 to 100.77 )  
  88.90  
  ( 57.65 to 120.14 )  
  109.81  
  ( 81.05 to 138.57 )  


Statistical Analysis 1 for Recovery Time From Hypoglycemia to Euglycemia
Groups [1] Placebo vs. Glimepiride 2 mg
Mean Difference (Final Values) [2] 14.41
90% Confidence Interval ( -22.98 to 51.80 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
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[2] Other relevant estimation information:
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Statistical Analysis 2 for Recovery Time From Hypoglycemia to Euglycemia
Groups [1] Placebo vs. Glimepiride 4 mg
Mean Difference (Final Values) [2] 35.33
90% Confidence Interval ( -2.08 to 72.74 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
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2.  Primary:   Rate of Recovery From Hypoglycemia to Euglycemia   [ Time Frame: From 1 to 180 minutes post hypoglycemic clamp ]

3.  Primary:   Incremental Weighted Average Blood Glucose Concentration Over 3 Hours of Hypoglycemic Recovery   [ Time Frame: From 1 to 180 minutes post hypoglycemic clamp ]


  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