Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1293 Compared With a Basal Insulin in Participants With Type 1 Diabetes (MK-1293-005) (NCT NCT02059174)
NCT ID: NCT02059174
Last Updated: 2018-09-05
Results Overview
Duration of Action (DOA) is defined as the length of time from dosing to End of Action. End of Action is defined as the time point at which plasma glucose has been above 150 mg/dL for 30 minutes and no glucose has been infused for 30 minutes. Median and max below are reported for the length of clamp duration (i.e. 30 hours).
COMPLETED
PHASE1
76 participants
Up to 30 hours postdose
2018-09-05
Participant Flow
Male and female participants with Type I diabetes mellitus between the ages of 18 and 65 years (inclusive) were enrolled in this trial in 1 clinical site in the United States.
Participant milestones
| Measure |
MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
Period 1
STARTED
|
37
|
39
|
|
Period 1
COMPLETED
|
37
|
37
|
|
Period 1
NOT COMPLETED
|
0
|
2
|
|
Period 2
STARTED
|
37
|
37
|
|
Period 2
COMPLETED
|
36
|
35
|
|
Period 2
NOT COMPLETED
|
1
|
2
|
|
Period 3
STARTED
|
36
|
35
|
|
Period 3
COMPLETED
|
35
|
35
|
|
Period 3
NOT COMPLETED
|
1
|
0
|
|
Period 4
STARTED
|
35
|
35
|
|
Period 4
COMPLETED
|
35
|
35
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
MK-1293 / EU-Lantus™ / MK-1293 / EU-Lantus™
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™ / MK-1293 / EU-Lantus™ / MK-1293
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
Period 1
Withdrawal by Subject
|
0
|
2
|
|
Period 2
Withdrawal by Subject
|
0
|
2
|
|
Period 2
Protocol Violation
|
1
|
0
|
|
Period 3
Physician Decision
|
1
|
0
|
Baseline Characteristics
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MK-1293 Compared With a Basal Insulin in Participants With Type 1 Diabetes (MK-1293-005)
Baseline characteristics by cohort
| Measure |
All Participants
n=76 Participants
MK-1293 or EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|
|
Age, Continuous
|
33.4 Years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 30 hours postdosePopulation: The Per-Protocol population consists of 75 participants, including the 70 with complete data across all 4 treatment periods and 5 participants with partial data. One participant was not included in the PP population due to a medical issue. All available data from 5 of the participants who discontinued the study were included in the analyses.
Duration of Action (DOA) is defined as the length of time from dosing to End of Action. End of Action is defined as the time point at which plasma glucose has been above 150 mg/dL for 30 minutes and no glucose has been infused for 30 minutes. Median and max below are reported for the length of clamp duration (i.e. 30 hours).
Outcome measures
| Measure |
MK-1293
n=74 Participants
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™
n=75 Participants
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
Comparison of MK-1293 and EU-Approved Lantus Duration of Pharmacodynamic Action During a 30-Hour Euglycemic Clamp Study
|
30 Hours
Interval 0.0 to 30.0
|
30 Hours
Interval 11.93 to 30.0
|
PRIMARY outcome
Timeframe: Up to 24 hours postdosePopulation: The Per-Protocol population included 70 participants with complete data and 5 participants with partial data. One participant was not included in the PP population due to a medical issue. Data from 5 discontinued participants were included in the analyses; data from 1 participant was not (incomplete clamp data, only out to 18.5 hours).
The area under the glucose infusion rate curve from hours 0 to 24 after injection (AUC\[GIR{0-24}\]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Outcome measures
| Measure |
MK-1293
n=74 Participants
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™
n=74 Participants
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over 24 Hours After Dosing (GIR-AUC0-24hr)
|
1470.07 mg/kg
Interval 1256.52 to 1683.63
|
1554.53 mg/kg
Interval 1334.03 to 1775.04
|
PRIMARY outcome
Timeframe: Up to 12 hours postdosePopulation: The Per-Protocol population consists of 75 participants, including the 70 with complete data across all 4 treatment periods and 5 participants with partial data. One participant was not included in the PP population due to a medical issue. All available data from 5 of the participants who discontinued the study were included in the analyses.
The area under the glucose infusion rate curve from hours 0 to 12 after injection (AUC\[GIR{0-12}\]) for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Outcome measures
| Measure |
MK-1293
n=74 Participants
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™
n=75 Participants
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the First 12 Hours After Dosing (GIR-AUC0-12hr)
|
659.38 mg/kg
Interval 557.84 to 760.92
|
736.31 mg/kg
Interval 625.22 to 847.41
|
PRIMARY outcome
Timeframe: From 12 to 24 hours postdosePopulation: The Per-Protocol population included 70 participants with complete data and 5 participants with partial data. One participant was not included in the PP population due to a medical issue. Data from 5 discontinued participants were included in the analyses; data from 1 participant was not (incomplete clamp data, only out to 18.5 hours).
The area under the glucose infusion rate curve from hours 12 to 24 after injection (AUC\[GIR{12-24}\]) for participants who received either MK-1293 or Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Outcome measures
| Measure |
MK-1293
n=74 Participants
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™
n=74 Participants
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
PD: Area Under the Glucose Infusion Rate Versus Time Curve Over the Second 12 Hours After Dosing (GIR-AUC12-24hr)
|
811.43 mg/kg
Interval 689.89 to 932.98
|
818.20 mg/kg
Interval 700.4 to 936.01
|
PRIMARY outcome
Timeframe: Up to 30 hours postdosePopulation: The Per-Protocol population included 70 participants with complete data and 5 participants with partial data. One participant was not included in the PP population due to a medical issue. Data from 5 discontinued participants were included in the analyses; data from 1 participant was not (incomplete clamp data, only out to 18.5 hours).
Maximum glucose infusion rate (GIR\[max\]) based on smoothed data for participants who received either MK-1293 or EU-Lantus™ administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design was measured from blood samples obtained during a euglycemic clamp procedure.
Outcome measures
| Measure |
MK-1293
n=74 Participants
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™
n=74 Participants
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
PD: Maximum Glucose Infusion Rate (GIRmax)
|
2.34 mg/kg/min
Interval 2.11 to 2.57
|
2.43 mg/kg/min
Interval 2.18 to 2.68
|
PRIMARY outcome
Timeframe: Up to 24 hours postdosePopulation: The Per-Protocol population consists of 75 participants, including the 70 with complete data across all 4 treatment periods and 5 participants with partial data. One participant was not included in the PP population due to a medical issue. All available data from 5 of the participants who discontinued the study were included in the analyses.
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Analysis was performed on log scale with results back transformed to the original scale
Outcome measures
| Measure |
MK-1293
n=74 Participants
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™
n=75 Participants
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
M1 Glargine Metabolite Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC0-24)
|
6530 pg∙hr/mL
Interval 5967.0 to 7145.0
|
6763 pg∙hr/mL
Interval 6162.0 to 7423.0
|
PRIMARY outcome
Timeframe: Up to 24 hours postdosePopulation: The Per-Protocol population consists of 75 participants, including the 70 with complete data across all 4 treatment periods and 5 participants with partial data. One participant was not included in the PP population due to a medical issue. All available data from 5 of the participants who discontinued the study were included in the analyses.
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Analysis was performed on log scale with results back transformed to original scale.
Outcome measures
| Measure |
MK-1293
n=74 Participants
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™
n=75 Participants
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
M1 Glargine Metabolite PK: Maximum Plasma Concentration (Cmax)
|
372 pg/mL
Interval 339.0 to 408.0
|
382 pg/mL
Interval 350.0 to 416.0
|
SECONDARY outcome
Timeframe: Up to 12 hours postdosePopulation: The Per-Protocol population consists of 75 participants, including the 70 with complete data across all 4 treatment periods and 5 participants with partial data. One participant was not included in the PP population due to a medical issue. All available data from 5 of the participants who discontinued the study were included in the analyses.
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC0-12 is a measure of the total amount of drug in the plasma from the dose to Hour 12. Analysis was performed on log scale with results back transformed to original scale.
Outcome measures
| Measure |
MK-1293
n=74 Participants
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™
n=75 Participants
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the First 12 Hours After Dosing (AUC0-12)
|
2981 pg∙hr/mL
Interval 2714.0 to 3274.0
|
3251 pg∙hr/mL
Interval 2968.0 to 3562.0
|
SECONDARY outcome
Timeframe: From 12 to 24 hours postdosePopulation: The Per-Protocol population consists of 75 participants, including the 70 with complete data across all 4 treatment periods and 5 participants with partial data. One participant was not included in the PP population due to a medical issue. All available data from 5 of the participants who discontinued the study were included in the analyses.
M1 glargine is the dominant circulating glargine-derived insulin metabolite after subcutaneous injection and it is pharmacologically active. AUC12-24 is a measure of the total amount of drug in the plasma from Hour 12 to Hour 24. Analysis was performed on log scale with results back transformed to original scale.
Outcome measures
| Measure |
MK-1293
n=74 Participants
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
EU-Lantus™
n=75 Participants
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between each treatment period
|
|---|---|---|
|
M1 Glargine Metabolite PK: Area Under the Plasma Concentration Versus Time Curve Over the Second 12 Hours After Dosing (AUC12-24)
|
3510 pg∙hr/mL
Interval 3205.0 to 3845.0
|
3522 pg∙hr/mL
Interval 3228.0 to 3844.0
|
Adverse Events
MK-1293 0.4 Units/kg SC
EU-Lantus™ 0.4 Units.kg SC
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
MK-1293 0.4 Units/kg SC
n=74 participants at risk
MK-1293 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between treatment periods
|
EU-Lantus™ 0.4 Units.kg SC
n=76 participants at risk
EU-Lantus™ 0.4 units/kg administered subcutaneously on Day 1 in 2 out of 4 study periods in a replicate crossover design with a minimum of 7 days between treatment periods
|
|---|---|---|
|
General disorders
Injection site haemorrhage
|
4.1%
3/74 • Number of events 3 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
5.3%
4/76 • Number of events 4 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
|
General disorders
Vessel puncture site haemorrhage
|
8.1%
6/74 • Number of events 6 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
6.6%
5/76 • Number of events 9 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
|
General disorders
Vessel puncture site pain
|
1.4%
1/74 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
5.3%
4/76 • Number of events 4 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
|
General disorders
Vessel puncture site reaction
|
8.1%
6/74 • Number of events 6 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
7.9%
6/76 • Number of events 6 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
8.1%
6/74 • Number of events 7 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
1.3%
1/76 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
74.3%
55/74 • Number of events 120 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
65.8%
50/76 • Number of events 111 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
|
Nervous system disorders
Headache
|
4.1%
3/74 • Number of events 3 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
7.9%
6/76 • Number of events 7 • Up to 14 days after the last dose of study drug (Up to 7 weeks)
All Subjects as Treated population included all participants who received at least one dose of an investigational drug. Two participants discontinued after Period 1 (EU-Lantus) so did not cross-over to MK-1293.
|
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 trial 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
- Publication restrictions are in place
Restriction type: OTHER