Trial Outcomes & Findings for A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED) (NCT NCT00902161)
NCT ID: NCT00902161
Last Updated: 2015-07-03
Results Overview
Rt(65) defined as the time to recover from hypoglycemia (blood glucose level of 50 mg/dL) to an arterialized venous blood glucose of 65 mg/dL. At t= -60 minutes on the morning of Day 1 (Visit 6) or Day 22 (Visit 8), a hypoglycemic clamp was used via an increased insulin infusion rate to achieve blood glucose concentrations of 50 mg/dL (2.8 mmol/L) within \~30-90 minutes. At the end of the 30-minute hypoglycemic clamp interval, insulin and glucose infusions were terminated, and the time to recover from hypoglycemia to 65 mg/dL Rt(65) was determined. Rt(65) was followed up to 270 minutes
COMPLETED
PHASE1
22 participants
From the time of hypoglycemic clamp (t=0 minutes) through 270 minutes
2015-07-03
Participant Flow
Participant milestones
| Measure |
Propanolol + MK0893 / Propanolol + Placebo
After a 4 week wash-out period with a 4-week propanolol run-on, single dose MK0893 was added on Day -1 of Period 1 (Study Visit 6) and propanolol was continued. After Period 1, participants underwent a 3-week wash-out while continuing to receive propanolol alone. Following the washout, participants were treated with a single dose of MK0893-matched placebo on Day 21 (Visit 8) while continuing on propanolol.
|
Propanolol + Placebo / Propanolol + MK0893
After a 4 week wash-out period with a 4-week propanolol run-on, MK0893-matched placebo was added on Day -1 of Period 1 (Study Visit 6) and propanolol was continued. After Period 1, participants underwent a 3-week wash-out while continuing to receive propanolol alone. Following the washout, participants were treated with a single dose of MK0893 on Day 21 (Visit 8) while continuing on propanolol.
|
Propanolol Alone
Participants received treatment with propanolol alone during a 4 week run-on before the 1st clamp procedure at Visit 6, and during a 3 week washout between clamp procedures at Visits 6 (Period 1) and 8 (Period 2). Overall, participants were treated with propranolol for approximately 7 weeks (from propranol titration through Visit 8 clamp procedures).
|
|---|---|---|---|
|
Pre-study Washout/Propanolol Run-in
STARTED
|
0
|
0
|
22
|
|
Pre-study Washout/Propanolol Run-in
COMPLETED
|
0
|
0
|
22
|
|
Pre-study Washout/Propanolol Run-in
NOT COMPLETED
|
0
|
0
|
0
|
|
Period 1
STARTED
|
12
|
10
|
0
|
|
Period 1
COMPLETED
|
12
|
10
|
0
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
|
Post-clamp Washout
STARTED
|
0
|
0
|
22
|
|
Post-clamp Washout
COMPLETED
|
0
|
0
|
22
|
|
Post-clamp Washout
NOT COMPLETED
|
0
|
0
|
0
|
|
Period 2
STARTED
|
8
|
9
|
0
|
|
Period 2
COMPLETED
|
8
|
9
|
0
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Single-Dose Crossover Study of MK0893 in Patients With Type 2 Diabetes (0893-019 AM4)(COMPLETED)
Baseline characteristics by cohort
| Measure |
MK0893 + Propanolol
n=12 Participants
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Placebo + Propanolol
n=10 Participants
Participants received a single dose of MK0893-matched placebo added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.3 years
STANDARD_DEVIATION 5.66 • n=99 Participants
|
48.5 years
STANDARD_DEVIATION 6.88 • n=107 Participants
|
50.0 years
STANDARD_DEVIATION 6.26 • n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: From the time of hypoglycemic clamp (t=0 minutes) through 270 minutesPopulation: 21 participants who received MK0893 + Propanolol while on study had data available, and 17 participants who received Placebo + Propanolol while on study had data available
Rt(65) defined as the time to recover from hypoglycemia (blood glucose level of 50 mg/dL) to an arterialized venous blood glucose of 65 mg/dL. At t= -60 minutes on the morning of Day 1 (Visit 6) or Day 22 (Visit 8), a hypoglycemic clamp was used via an increased insulin infusion rate to achieve blood glucose concentrations of 50 mg/dL (2.8 mmol/L) within \~30-90 minutes. At the end of the 30-minute hypoglycemic clamp interval, insulin and glucose infusions were terminated, and the time to recover from hypoglycemia to 65 mg/dL Rt(65) was determined. Rt(65) was followed up to 270 minutes
Outcome measures
| Measure |
MK0893 + Propanolol
n=21 Participants
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Placebo + Propanolol
n=17 Participants
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Propanolol Alone
Participants received treatment with propanolol alone during a 4 week washout before the 1st clamp procedure at Visit 6, and during a 3 week washout between clamp procedures at Visits 6 (Period 1) and 8 (Period 2). Overall, participants were treated with propranolol for approximately 7 weeks (from propranolol titration through Visit 8 clamp procedures).
|
|---|---|---|---|
|
Recovery Time (Rt[65] From Insulin-induced Hypoglycemia
|
103 minutes
Interval 88.0 to 118.0
|
71 minutes
Interval 55.0 to 88.0
|
—
|
SECONDARY outcome
Timeframe: From time of MK0893 administration through 24 hours post-dosePopulation: Data from the first 15 participants who completed the study were used for the pharmacokinetic analysis.
Cmax was the maximum or "peak" concentration of MK0893 observed after its administration. Approximate C(ave 8-12) was the MK0893 concentration average over 8-12 hours post-dose and was computed as the Area Under the Curve over 8-12 hours post-dose (AUC \[8-12\]) ÷ 4
Outcome measures
| Measure |
MK0893 + Propanolol
n=15 Participants
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Placebo + Propanolol
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Propanolol Alone
Participants received treatment with propanolol alone during a 4 week washout before the 1st clamp procedure at Visit 6, and during a 3 week washout between clamp procedures at Visits 6 (Period 1) and 8 (Period 2). Overall, participants were treated with propranolol for approximately 7 weeks (from propranolol titration through Visit 8 clamp procedures).
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) and Concentration Average Over 8-12 Hours (C[Ave] 8-12 hr) Post Single Dose MK0893
Cmax
|
29.18 uM
Standard Deviation 6.51
|
—
|
—
|
|
Maximum Plasma Concentration (Cmax) and Concentration Average Over 8-12 Hours (C[Ave] 8-12 hr) Post Single Dose MK0893
C(ave) 8-12hr
|
26.75 uM
Standard Deviation 6.04
|
—
|
—
|
SECONDARY outcome
Timeframe: From time of MK0893 administration through estimated 32 hours post-dosePopulation: Data from the first 15 participants who completed the study were used for the pharmacokinetic analysis.
Plasma concentration of single dose MK0893 was measured from time of administration to 24 hours post-dose and extrapolated out to 32 hours post-dose using the plasma concentration vs. time curve
Outcome measures
| Measure |
MK0893 + Propanolol
n=15 Participants
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Placebo + Propanolol
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Propanolol Alone
Participants received treatment with propanolol alone during a 4 week washout before the 1st clamp procedure at Visit 6, and during a 3 week washout between clamp procedures at Visits 6 (Period 1) and 8 (Period 2). Overall, participants were treated with propranolol for approximately 7 weeks (from propranolol titration through Visit 8 clamp procedures).
|
|---|---|---|---|
|
Plasma Concentration at 32 Hours (C[32hr]) Post Single Dose MK0893
|
23.69 nM
Standard Deviation 4.86
|
—
|
—
|
SECONDARY outcome
Timeframe: From time of administration of study treatment through end of Post-Study (up to 21 days after administration of last dose of study treatment).Population: All treated participants
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. This also included any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product.
Outcome measures
| Measure |
MK0893 + Propanolol
n=22 Participants
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Placebo + Propanolol
n=22 Participants
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Propanolol Alone
n=22 Participants
Participants received treatment with propanolol alone during a 4 week washout before the 1st clamp procedure at Visit 6, and during a 3 week washout between clamp procedures at Visits 6 (Period 1) and 8 (Period 2). Overall, participants were treated with propranolol for approximately 7 weeks (from propranolol titration through Visit 8 clamp procedures).
|
|---|---|---|---|
|
Number of Participants With An Adverse Event (AE)
|
10 participants
|
4 participants
|
9 participants
|
SECONDARY outcome
Timeframe: From time of first administration of study treatment to time of last administration of study treatment (up to Day 21)Population: All treated participants
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. This also included any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product.
Outcome measures
| Measure |
MK0893 + Propanolol
n=22 Participants
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Placebo + Propanolol
n=22 Participants
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Propanolol Alone
n=22 Participants
Participants received treatment with propanolol alone during a 4 week washout before the 1st clamp procedure at Visit 6, and during a 3 week washout between clamp procedures at Visits 6 (Period 1) and 8 (Period 2). Overall, participants were treated with propranolol for approximately 7 weeks (from propranolol titration through Visit 8 clamp procedures).
|
|---|---|---|---|
|
Number of Participants Who Discontinued Study Treatment Due To AEs
|
1 participants
|
0 participants
|
0 participants
|
Adverse Events
MK0893 + Propanolol
Placebo + Propanolol
Propanolol Alone
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
MK0893 + Propanolol
n=22 participants at risk
Participants received a single dose of MK0893 added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Placebo + Propanolol
n=22 participants at risk
Participants received a single dose of MK0893-matched placebo added to a background of propanolol at either Visit 6 (Day -1) or Visit 8 (Day 21).
|
Propanolol Alone
n=22 participants at risk
Participants received treatment with propanolol alone during a 4 week washout before the 1st clamp procedure at Visit 6, and during a 3 week washout between clamp procedures at Visits 6 (Period 1) and 8 (Period 2). Overall, participants were treated with propranolol for approximately 7 weeks (from propranolol titration through Visit 8 clamp procedures).
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Iron Deficiency Anaemia
|
4.5%
1/22 • Number of events 1
|
9.1%
2/22 • Number of events 2
|
0.00%
0/22
|
|
Cardiac disorders
Arrhythmia Supraventricular
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
0.00%
0/22
|
|
Eye disorders
Vision Blurred
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
0.00%
0/22
|
|
Gastrointestinal disorders
Abdominal Pain
|
9.1%
2/22 • Number of events 2
|
0.00%
0/22
|
0.00%
0/22
|
|
Gastrointestinal disorders
Diarrhoea
|
18.2%
4/22 • Number of events 4
|
0.00%
0/22
|
0.00%
0/22
|
|
Gastrointestinal disorders
Nausea
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
|
General disorders
Chest Discomfort
|
0.00%
0/22
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
|
General disorders
Chest Pain
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
0.00%
0/22
|
|
General disorders
Fatigue
|
0.00%
0/22
|
0.00%
0/22
|
13.6%
3/22 • Number of events 3
|
|
General disorders
Feeling Hot
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
0.00%
0/22
|
|
Infections and infestations
Gastroenteritis Viral
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
|
Injury, poisoning and procedural complications
Wrist Fracture
|
0.00%
0/22
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
|
Investigations
Haematocrit Decreased
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
0.00%
0/22
|
|
Investigations
Haemoglobin Decreased
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/22
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Joint Effusion
|
0.00%
0/22
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
|
Nervous system disorders
Dizziness Postural
|
0.00%
0/22
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
|
Nervous system disorders
Headache
|
9.1%
2/22 • Number of events 2
|
0.00%
0/22
|
13.6%
3/22 • Number of events 3
|
|
Nervous system disorders
Somnolence
|
0.00%
0/22
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/22
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
4.5%
1/22 • Number of events 1
|
4.5%
1/22 • Number of events 1
|
0.00%
0/22
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
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. SPONSOR review can be expedited to meet publication guidelines.
- Publication restrictions are in place
Restriction type: OTHER