Trial Outcomes & Findings for Effects of Glimepiride on Recovery From Hypoglycemia in Participants With Type 2 Diabetes Mellitus (MK-0000-253) (NCT NCT01614769)

Last Updated: 2018-08-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

From 1 to 180 minutes post hypoglycemic clamp

Results posted on

2018-08-16

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Period 1 STARTED	2	1	2	2	1	2
Period 1 COMPLETED	1	1	2	0	1	1
Period 1 NOT COMPLETED	1	0	0	2	0	1
7-Day Washout STARTED	1	1	2	0	1	1
7-Day Washout COMPLETED	1	1	2	0	1	1
7-Day Washout NOT COMPLETED	0	0	0	0	0	0
Period 2 STARTED	1	1	2	0	1	1
Period 2 COMPLETED	1	1	2	0	1	1
Period 2 NOT COMPLETED	0	0	0	0	0	0
Period 3 STARTED	1	1	2	0	1	1
Period 3 COMPLETED	1	1	1	0	1	1
Period 3 NOT COMPLETED	0	0	1	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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 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 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.
Period 1 Discontinued due to Hypoglycemia	0	0	1	1
Period 1 Protocol Violation	0	0	1	0
Period 1 Withdrawal by Subject	1	0	0	0
Period 3 Withdrawal by Subject	0	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=10 Participants All randomized participants
Age, Continuous	49.3 Years STANDARD_DEVIATION 5.5 • n=113 Participants
Sex: Female, Male Female	4 Participants n=113 Participants
Sex: Female, Male Male	6 Participants n=113 Participants

PRIMARY outcome

Timeframe: From 1 to 180 minutes post hypoglycemic clamp

Population: The per-protocol population consisting of participants who received drug and completed the necessary post treatment measurements for at least one treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants received placebo in a treatment period.	Glimepiride 2 mg n=5 Participants Participants received 2 mg Glimepiride in a treatment period.	Glimepiride 4 mg n=6 Participants Participants received 4 mg Glimepiride in a treatment period.
Recovery Time From Hypoglycemia to Euglycemia	74.49 Minutes Interval 48.2 to 100.77	88.90 Minutes Interval 57.65 to 120.14	109.81 Minutes Interval 81.05 to 138.57

PRIMARY outcome

Timeframe: From 1 to 180 minutes post hypoglycemic clamp

Population: The per-protocol population consisting of participants who received drug and completed the necessary post treatment measurements for at least one treatment period.

The rate of recovery is the difference in concentration between blood glucose at euglycemia and at the end of the hypoglycemic clamp, divided by the recovery time.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants received placebo in a treatment period.	Glimepiride 2 mg n=5 Participants Participants received 2 mg Glimepiride in a treatment period.	Glimepiride 4 mg n=6 Participants Participants received 4 mg Glimepiride in a treatment period.
Rate of Recovery From Hypoglycemia to Euglycemia	0.32 mg/dL/minute Interval 0.24 to 0.4	0.22 mg/dL/minute Interval 0.12 to 0.31	0.19 mg/dL/minute Interval 0.1 to 0.27

PRIMARY outcome

Timeframe: From 1 to 180 minutes post hypoglycemic clamp

Population: The per-protocol population consisting of participants who received drug and completed the necessary post treatment measurements for at least one treatment period.

The incremental weighted average qualitatively assesses overall hypoglycemic recovery by measuring mean glycemia over the 3 hour recovery period. Blood glucose measured at the release of the hypoglycemic clamp, considered the baseline value, was subtracted from blood glucose values measured over the ensuing 3 hours of hypoglycemic recovery. These differences from baseline were averaged to calculate the incremental weighted average blood glucose concentration.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants received placebo in a treatment period.	Glimepiride 2 mg n=5 Participants Participants received 2 mg Glimepiride in a treatment period.	Glimepiride 4 mg n=6 Participants Participants received 4 mg Glimepiride in a treatment period.
Incremental Weighted Average Blood Glucose Concentration Over 3 Hours of Hypoglycemic Recovery	22.61 mg/dL Interval 17.55 to 27.68	17.58 mg/dL Interval 11.78 to 23.38	15.34 mg/dL Interval 9.94 to 20.75

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Glimepiride 2 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Glimepiride 4 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=9 participants at risk Participants received placebo in a treatment period.	Glimepiride 2 mg n=6 participants at risk Participants received 2 mg Glimepiride in a treatment period.	Glimepiride 4 mg n=7 participants at risk Participants received 4 mg Glimepiride in a treatment period.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/9 • Up to 14 days after last dose of study drug	16.7% 1/6 • Number of events 1 • Up to 14 days after last dose of study drug	0.00% 0/7 • Up to 14 days after last dose of study drug
Gastrointestinal disorders Constipation	11.1% 1/9 • Number of events 1 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	0.00% 0/7 • Up to 14 days after last dose of study drug
Gastrointestinal disorders Nausea	0.00% 0/9 • Up to 14 days after last dose of study drug	33.3% 2/6 • Number of events 2 • Up to 14 days after last dose of study drug	0.00% 0/7 • Up to 14 days after last dose of study drug
Gastrointestinal disorders Vomiting	0.00% 0/9 • Up to 14 days after last dose of study drug	16.7% 1/6 • Number of events 1 • Up to 14 days after last dose of study drug	0.00% 0/7 • Up to 14 days after last dose of study drug
General disorders Asthenia	0.00% 0/9 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	14.3% 1/7 • Number of events 1 • Up to 14 days after last dose of study drug
General disorders Oedema peripheral	11.1% 1/9 • Number of events 1 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	0.00% 0/7 • Up to 14 days after last dose of study drug
Infections and infestations Nasopharyngitis	0.00% 0/9 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	14.3% 1/7 • Number of events 1 • Up to 14 days after last dose of study drug
Investigations Body temperature increased	11.1% 1/9 • Number of events 1 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	0.00% 0/7 • Up to 14 days after last dose of study drug
Metabolism and nutrition disorders Hypoglycaemia	11.1% 1/9 • Number of events 1 • Up to 14 days after last dose of study drug	16.7% 1/6 • Number of events 1 • Up to 14 days after last dose of study drug	14.3% 1/7 • Number of events 1 • Up to 14 days after last dose of study drug
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 1/9 • Number of events 1 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	0.00% 0/7 • Up to 14 days after last dose of study drug
Nervous system disorders Dizziness	11.1% 1/9 • Number of events 1 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	0.00% 0/7 • Up to 14 days after last dose of study drug
Nervous system disorders Dizziness postural	11.1% 1/9 • Number of events 1 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	0.00% 0/7 • Up to 14 days after last dose of study drug
Nervous system disorders Headache	22.2% 2/9 • Number of events 2 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	14.3% 1/7 • Number of events 1 • Up to 14 days after last dose of study drug
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/9 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	14.3% 1/7 • Number of events 1 • Up to 14 days after last dose of study drug
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/9 • Up to 14 days after last dose of study drug	0.00% 0/6 • Up to 14 days after last dose of study drug	14.3% 1/7 • Number of events 1 • Up to 14 days after last dose of study drug