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Study of the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Participants With Type 2 Diabetes Mellitus (MK-8521-003)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01982630
Collaborator
(none)
87
Enrollment
8
Arms
10.8
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This study will evaluate the safety, efficacy, and pharmacokinetics of MK-8521 given once daily compared to placebo and another diabetes drug in participants with Type 2 diabetes mellitus (T2DM).

This study was modified by a protocol amendment to a 2-part trial to further test the safety and tolerability of MK-8521 at higher doses and to compare MK-8521 pharmacokinetics between participants with T2DM and healthy participants. An additional cohort of T2DM participants and a cohort of non-diabetic obese participants has been added.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
87 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase Ib, Multicenter, Placebo and Active- Comparator-Controlled, Randomized, Double-Blind, Clinical Trial to Evaluate the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Subjects With Type 2 Diabetes Mellitus
Actual Study Start Date :
Nov 7, 2013
Actual Primary Completion Date :
Oct 3, 2014
Actual Study Completion Date :
Oct 3, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: MK-8521 64/120 μg/day

Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14.

Drug: MK-8521
Experimental: Part 1: MK-8521 34/72 μg/day

T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.

Drug: MK-8521
Active Comparator: Part 1: Liraglutide 0.6/1.2/1.8 mg/day

T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14.

Drug: Liraglutide
Placebo Comparator: Part 1: Placebo for MK-8521

T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days.

Drug: Placebo
Experimental: Part 2: MK-8521 64/120/180/240/300 µg/day-T2DM

T2DM participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29.

Drug: MK-8521
Active Comparator: Part 2: Liraglutide 0.6/1.2/1.8 mg/day-T2DM

T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29.

Drug: Liraglutide
Placebo Comparator: Part 2: Placebo for MK-8521-T2DM

T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.

Drug: Placebo
Experimental: Part 2: MK-8521 64/120 µg/day-Non-Diabetic Overweight/Obese

Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 µg starting at 64 µg and increasing to 120 µg on Day 8. The total number of dosing days was 14.

Drug: MK-8521

Outcome Measures

Primary Outcome Measures

  1. Number of Participants Experiencing Adverse Events (AEs) in Part 1 [Up to approximately 42 days]

    An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.

  2. Number of Participants Experiencing Adverse Events (AEs) in Part 2 [Up to approximately 57 days]

    An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.

  3. Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 1 [Up to approximately 14 days]

    An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.

  4. Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 2 [Up to approximately 29 days]

    An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.

  5. Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Baseline (predose Day 1) and up to 24 hours post Day 7 dose]

    Semi-recumbent heart rate was assessed at baseline on Day 1; Day 7 at predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose; and prior to dosing on Day 8. Heart rate was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr was calculated as the area under the measurement-time curve (AUC) divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.

  6. Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 7 dose]

    Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.

  7. Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Baseline (predose Day 1) and up to 24 hours post Day 14 dose]

    Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.

  8. Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 14 dose]

    Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.

  9. Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 19 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 19 dose]

    Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, 16, hours post dose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 19 minus baseline where baseline was defined as predose on Day 1.

  10. Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 24 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 24 dose]

    Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 24 minus baseline where baseline was defined as predose on Day 1.

  11. Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 29 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 29 dose]

    Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose, 2, 4, 6, 8, 12, 16 and 24 hours postdose. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 29 minus baseline where baseline was defined as predose on Day 1.

  12. Change From Baseline in Peak Heart Rate (PHR) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 7 dose]

    PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 7 minus baseline where baseline was defined as predose on Day 1.

  13. Change From Baseline in Peak Heart Rate (PHR) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 14 dose]

    PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 14 minus baseline where baseline was defined as predose on Day 1.

  14. Change From Baseline in Peak Heart Rate (PHR) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 19 dose]

    PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 19 minus baseline where baseline was defined as predose on Day 1.

  15. Change From Baseline in Peak Heart Rate (PHR) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 24 dose]

    PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 24 minus baseline where baseline was defined as predose on Day 1.

  16. Change From Baseline in Peak Heart Rate (PHR) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and up to 24 hours post Day 29 dose]

    PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose 2, 4, 6, 8, 12, 16, and 24 hours post dose. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 29 minus baseline where baseline was defined as predose on Day 1.

  17. Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 7 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and Day 8 (24 hours after Day 7)]

    Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 7 dose (predose Day 8) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  18. Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 14 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and Day 15 (24 hours after Day 14)]

    Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 14 dose (predose Day 15) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  19. Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 19 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and Day 20 (24 hours after Day 19)]

    Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 19 dose (predose Day 20) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  20. Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 24 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and Day 25 (24 hours after Day 24)]

    Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 24 dose (predose Day 25) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  21. Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 29 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose Day 1) and Day 30 (24 hours after Day 29)]

    Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 29 dose minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.

  22. Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1, 7, and 14]

    AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.

  23. Maximum Concentration (Cmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7]

    Cmax was the maximum observed concentration of MK-8521 in plasma after administration. Plasma samples were collected from predose to 24 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.

  24. Maximum Concentration (Cmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14]

    Cmax was the maximum observed concentration of MK-8521 in plasma after administration on Day 14. Plasma samples were collected from predose to 120 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.

  25. Trough Concentration (Ctrough) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose on Days 2, 7, and 14]

    Ctrough was the lowest observed concentration of MK-8521 in plasma. Plasma samples were collected predose on Day 2 (sampled after the Day 1 dose and prior to Day 2 dose), 7, and 14 for determination of Ctrough. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Ctrough is presented as geometric mean and percent coefficient of variation of geometric mean.

  26. Time to Maximum Concentration (Tmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7]

    Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 24 hours postdose for determination of Tmax. Tmax is presented as median with a full range.

  27. Time to Maximum Concentration (Tmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14]

    Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 120 hours postdose for determination of Tmax. Tmax is presented as median with a full range.

  28. Apparent Terminal Half Life (t1/2) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7]

    t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 24 hours postdose for determination of t1/2. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.

  29. Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14]

    t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 120 hours postdose for determination of t1/2. t1/2 was measured on Day 14 which is the longest time point for sampling for T2DM participants in Part 1. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.

  30. Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7]

    Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio with a full range.

  31. Accumulation Ratio of the Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7]

    Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of Cmax. The geometric mean accumulation ratio was calculated as Day 7 Cmax/Day 1 Cmax and presented as geometric mean ratio with a full range.

  32. Accumulation Ratio of the Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose on Days 2 and 7]

    Plasma samples were collected predose on Days 2 (sampled after the Day 1 dose and prior to Day 2 dose) and 7 for determination of the accumulation ratio of Ctrough. The geometric mean accumulation ratio was calculated as Day 7 Ctrough/Day 1 Ctrough (sampled after the Day 1 dose and prior to Day 2 dose) and presented as geometric mean ratio with a full range.

  33. Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 [Predose and 1, 2, 6, 10, 16, and 24 hours postdose on Days 1, 7, and 14]

    AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.

  34. Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 [Predose and 1, 2, 6, 10, 16, and 24 hours post-dose on Days 1 and 7]

    Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio and percent geometric coefficient of variation.

Secondary Outcome Measures

  1. Change From Baseline in Fasting Plasma Glucose (FPG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose on Days 1 (baseline) and 7]

    FPG was measured predose on Days 1 and 7. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 7. FPG is presented as mean change from baseline with a standard error.

  2. Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Predose on Days 1 (baseline) and 14]

    FPG was measured predose on Days 1 and 14. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 14. FPG is presented as mean change from baseline with a standard error.

  3. Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Baseline (predose and before food on Day 1) and up to 24 hours post Day 7 dose]

    The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Blood samples for glucose were collected immediately prior to, and after each meal. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Blood for plasma glucose concentrations was obtained at predose Day 1 at pre meal (breakfast), 0.5, 1, 2, 3, 4 (pre lunch), 4.5, 5, 6, 7, 10 (pre dinner), 10.5, 11, 12, 13, 15 and 23 hours post breakfast meal; and on Day 7 at 1 (pre breakfast), 1.5, 2, 3, 4, 5 (pre lunch), 5.5, 6, 7, 8, 11 (pre dinner), 11.5, 12, 13, 14, 16, 24 hours post dose. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with fixed effects for treatment, day and treatment by day interaction, a random effect for participant, and baseline 24-hour WMG as a covariate. WMG is presented as least squares mean with a 95% confidence interval.

  4. Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1 [Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose]

    The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Blood samples for glucose were collected immediately prior to and after each meal. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Blood for plasma glucose concentrations was obtained on Day -1 at pre meal (breakfast), 0.5, 1, 2, 3, 4 (pre lunch), 4.5, 5, 6, 7, 10 (pre dinner), 10.5, 11, 12, 13, 15 and 23 hours post breakfast meal; and on Day 14 at 1 (pre breakfast), 1.5, 2, 3, 4, 5 (pre lunch), 5.5, 6, 7, 8, 11(pre dinner), 11.5, 12, 13, 14, 16, 24 hours post dose. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with fixed effects for treatment, day and treatment by day interaction, a random effect for participant, and baseline 24-hour WMG as a covariate. WMG is presented as least squares mean with a 95% confidence interval.

  5. Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Predose on Days 1 (baseline) and 14]

    FPG was measured predose on Days 1 and 14. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 14. FPG is presented as least squares mean change from baseline with a 95% confidence interval.

  6. Change From Baseline in Fasting Plasma Glucose (FPG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Predose on Days 1 (baseline) and 19]

    FPG was measured predose on Days 1 and 19. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 19. FPG is presented as least squares mean change from baseline with a 95% confidence interval.

  7. Change From Baseline in Fasting Plasma Glucose (FPG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Predose on Days 1 (baseline) and 24]

    FPG was measured predose on Days 1 and 24. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 24. FPG is presented as least squares mean change from baseline with a 95% confidence interval.

  8. Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Predose on Days 1 (baseline) and 29]

    FPG was measured predose on Days 1 and 29. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 29. FPG is presented as least squares mean change from baseline with a 95% confidence interval.

  9. Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose]

    The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 14 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 14 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.

  10. Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose and before food on Day 1) and up to 24 hours post Day 19 dose]

    The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 19 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 19 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.

  11. Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose and before food on Day 1) and up to 24 hours post Day 24 dose]

    The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 24 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 24 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.

  12. Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Baseline (predose and before food on Day 1) and up to 24 hours post Day 29 dose]

    The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 29 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 29 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.

  13. Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 [Predose and 1, 2, 6, 10, 16, 24 hours post dose on Days 1, 7, 14, 19, 24 (T2DM) and Days 1 and 7 (Non-Diabetic Overweight/Obese); predose and 1, 2, 6, 10, 16, 24, 72, 96. and 120 hours post dose on Day 14 (Non-Diabetic Overweight/Obese) and Day 29 (T2DM).]

    Cmax was the maximum observed concentration of MK-8521 in plasma after administration. Plasma samples were collected from predose to 120 hours postdose for determination of Cmax. Per protocol, Cmax in the non-diabetic overweight/obese participants was not measured on Days 19, 24, and 29 because they only received 14 days of treatment. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.

  14. Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 [Predose on Days 2 (sampled 24 hours after Day 1 dose) and 7, 14, 19, 24, and 29]

    Ctrough was the lowest observed concentration of MK-8521 in plasma. Plasma samples were collected predose on Day 2 (sampled after the Day 1 dose and prior to Day 2 dose), 7, 14, 19, 24, and 29 for determination of Ctrough. Per protocol, Ctrough in the non-diabetic overweight/obese participants was not measured on Days 19, 24, and 29 because they only received 14 days of treatment. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Ctrough is presented as geometric mean and percent coefficient of variation of geometric mean.

  15. Time to Maximum Concentration (Tmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2 [Predose and 1, 2, 6, 10, 16, 24 hours post dose on Days 1, 7, 14, 19, 24 (T2DM) and Days 1 and 7 (Non-Diabetic Overweight/Obese); predose and 1, 2, 6, 10, 16, 24, 72, 96. and 120 hours post dose on Day 14 (Non-Diabetic Overweight/Obese) and Day 29 (T2DM).]

    Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 120 hours postdose for determination of Tmax. Per protocol, Tmax in the non-diabetic overweight/obese participants was not measured on Days 19, 24, and 29 because they only received 14 days of treatment. Tmax is presented as median with a full range.

  16. Apparent Terminal Half Life (t1/2) of MK-8521 on Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2 [Predose and 1, 2, 6, 10, 16, 24, 72, 96 and 120 hours post dose on Day 29]

    t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 120 hours postdose for determination of t1/2. Per protocol, t1/2 was measured on Day 29 which is the longest time point for sampling for T2DM participants 1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.

  17. Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Non-Diabetic Overweight/Obese Participants in Part 2 [Predose and 1, 2, 6, 10, 16, and 24 hours post dose on Day 14]

    t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 24 hours postdose for determination of t1/2. Per protocol, t1/2 was measured on Day 14 which is the longest time point for sampling for non-diabetic overweight/obese participants 1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

  • Male, or female of non-childbearing potential with Type 2 diabetes mellitus (Parts 1 and 2) or non-diabetic (Part 2)

  • Body mass index (BMI) between: ≥27 and ≤40 kg/m^2

  • A1C (average blood sugar for the past 2 to 3 months) value ≥7.0 and ≤11.0 % (Part 1) or ≥ 6.5 and ≤11.0 % (Part 2) at the time of screening (T2DM participants)

  • A1C value <5.7 at the time of screening (non-diabetic subjects in Part 2 only)

  • On a stable dose of metformin (≥1000 mg total daily dose) for at least 12 weeks at the time of screening (T2DM participants)

Exclusion Criteria:

  • Mentally or legally incapacitated

  • History of clinically significant psychiatric disorder of the last 5 years. Participants with situational depression may be enrolled in the trial at the discretion of the Investigator

  • History of Type 1 diabetes mellitus or a history of ketoacidosis

  • History of clinically significant gastrointestinal, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases

  • History of cardiovascular disease or cardiac conduction disorder

  • History of cancer (malignancy). Exceptions may include adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated ≥10 years prior to the pre-screening visit

  • History of proliferative diabetic retinopathy or maculopathy

  • Clinically significant diabetic autonomic neuropathy

  • QTc interval ≥470 msec (for males) or ≥480 msec (for females)

  • Clinical significant electrocardiogram (ECG) abnormality

  • Positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)

  • On a weight loss program and is not weight-stable (weight stable is defined history of <5% change in body weight in the last 3 months

  • On a weight loss medication or has undergone bariatric surgery

  • Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit

  • Participated in another investigational trial within 4 weeks prior to the pretrial (screening) visit

  • History of acute or chronic pancreatitis of any etiology

  • Mean value for triplicate semi-recumbent systolic blood pressure >160 mm Hg and/or diastolic blood pressure >90 mm Hg (after at least a 10-minute seated rest) and blood pressure is considered unlikely to be below these limits by Day-1 (Randomization) with initiation or adjustment of antihypertensive medication

  • Event of severe hypoglycemia with seizure or loss of consciousness in the past 12 months

  • Treated with anti-hyperglycemic agents other than metformin within the last 12 weeks

  • Previous exposure to any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g. Byetta™, Victoza™ or investigational agents)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01982630
Other Study ID Numbers:
  • 8521-003
First Posted:
Nov 13, 2013
Last Update Posted:
Mar 8, 2022
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Liraglutide

Study Results

Participant Flow

Recruitment Details This study had 2 parts: Part 1 evaluated MK-8521, placebo, and liraglutide in participants with Type 2 diabetes mellitus (T2DM); Part 2 evaluated MK-8521 at higher doses, liraglutide, and placebo in participants with T2DM and MK-8521 in non-diabetic, obese participants.
Pre-assignment Detail Participant flow, baseline characteristic, and outcome measure data are presented by study treatment sequence. Adverse events are presented by the individual doses contained in the study treatment sequence.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day Part 1: Liraglutide 0.6/1.2/1.8 mg/Day Part 1: Placebo for MK-8521 Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM Part 2: MK-8521 64/120 µg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days. T2DM participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 µg starting at 64 µg and increasing to 120 µg on Day 8. The total number of dosing days was 14.
Period Title: Overall Study
STARTED 10 8 13 9 19 14 6 8
Treated 9 8 11 9 18 14 6 8
COMPLETED 7 8 8 8 16 11 5 8
NOT COMPLETED 3 0 5 1 3 3 1 0

Baseline Characteristics

Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day Part 1: Liraglutide 0.6/1.2/1.8 mg/Day Part 1: Placebo for MK-8521 Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM Part 2: MK-8521 64/120 µg/Day-Non-Diabetic Overweight/Obese Total
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days. T2DM participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 µg starting at 64 µg and increasing to 120 µg on Day 8. The total number of dosing days was 14. Total of all reporting groups
Overall Participants 10 8 13 9 19 14 6 8 87
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
52.1
(8.6)
55.0
(6.4)
54.5
(8.8)
51.3
(9.0)
54.6
(6.0)
54.6
(7.9)
52.8
(6.9)
37.9
(14.1)
52.3
(9.4)
Sex: Female, Male (Count of Participants)
Female
5
50%
2
25%
5
38.5%
6
66.7%
11
57.9%
9
64.3%
2
33.3%
2
25%
42
48.3%
Male
5
50%
6
75%
8
61.5%
3
33.3%
8
42.1%
5
35.7%
4
66.7%
6
75%
45
51.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
8
80%
8
100%
12
92.3%
8
88.9%
11
57.9%
8
57.1%
4
66.7%
4
50%
63
72.4%
Not Hispanic or Latino
2
20%
0
0%
1
7.7%
0
0%
8
42.1%
6
42.9%
2
33.3%
4
50%
23
26.4%
Unknown or Not Reported
0
0%
0
0%
0
0%
1
11.1%
0
0%
0
0%
0
0%
0
0%
1
1.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
1
5.3%
0
0%
0
0%
0
0%
1
1.1%
Asian
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Black or African American
6
60%
0
0%
0
0%
1
11.1%
1
5.3%
4
28.6%
1
16.7%
0
0%
13
14.9%
White
4
40%
8
100%
13
100%
8
88.9%
17
89.5%
10
71.4%
5
83.3%
8
100%
73
83.9%
More than one race
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%

Outcome Measures

1. Primary Outcome
Title Number of Participants Experiencing Adverse Events (AEs) in Part 1
Description An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Time Frame Up to approximately 42 days

Outcome Measure Data

Analysis Population Description
The analysis population included all participants in Part 1 who received at least one dose of study drug.
Arm/Group Title Part 1: MK-8521 64 μg/Day Part 1: MK-8521 120 μg/Day Part 1: MK-8521 34 μg/Day Part 1: MK-8521 72 μg/Day Part 1: Liraglutide 0.6 mg/Day Part 1: Liraglutide 1.2 mg/Day Part 1: Liraglutide 1.8 mg/Day Part 1: Placebo for MK-8521
Arm/Group Description Type 2 Diabetes Mellitus (T2DM) participants received once daily subcutaneous MK-8521 64 μg/day on Days 1 to 7 as part of the MK-8521 64/120 μg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 120 μg/day on Days 8 to 14 as part of the MK-8521 64/120 μg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 34 μg/day on Days 1 to 7 as part of the MK-8521 34/72 μg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 72 μg/day on Days 8 to 14 as part of the MK-8521 34/72 μg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 0.6 mg on Day 1 and 2 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 1.2 mg on Days 3 to 7 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 1.8 mg on Days 8 to 14 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days.
Measure Participants 9 7 8 8 11 11 8 8
Count of Participants [Participants]
5
50%
5
62.5%
1
7.7%
4
44.4%
2
10.5%
7
50%
2
33.3%
5
62.5%
2. Primary Outcome
Title Number of Participants Experiencing Adverse Events (AEs) in Part 2
Description An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Time Frame Up to approximately 57 days

Outcome Measure Data

Analysis Population Description
The analysis population included all participants in Part 2 who received at least one dose of study drug.
Arm/Group Title Part 2: MK-8521 64 μg/Day Part 2: MK-8521 120 μg/Day Part 2: MK-8521 180 μg/Day Part 2: MK-8521 240 μg/Day Part 2: MK-8521 300 μg/Day Part 2: Liraglutide 0.6 mg/Day Part 2: Liraglutide 1.2 mg/Day Part 2: Liraglutide 1.8 mg/Day Part 2: Placebo for MK-8521-T2DM Part 2: MK-8521 64 µg/Day-Non-Diabetic Overweight/Obese Part 2: MK-8521 120 µg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Type 2 Diabetes Mellitus (T2DM) participants received once daily subcutaneous MK-8521 64 µg/day on Days 1 to 7 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 120 µg/day on Days 8 to 14 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 180 µg/day on Days 15 to 19 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 240 µg/day on Days 20 to 24 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 300 µg/day on Days 25 to 29 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 0.6 mg on Days 1 to 7 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 1.2 mg on Days 8 to 14 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 1.8 mg on Days 15 to 29 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 64 µg/day on Days 1 to 7 as part of the MK-8521 64/120 µg/day treatment group schedule. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 120 µg/day hon Days 8 to 14 as part of the MK-8521 64/120 µg/day treatment group schedule.
Measure Participants 18 18 18 18 15 14 13 13 6 8 8
Count of Participants [Participants]
8
80%
14
175%
6
46.2%
13
144.4%
8
42.1%
8
57.1%
8
133.3%
12
150%
3
3.4%
2
NaN
4
NaN
3. Primary Outcome
Title Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 1
Description An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Time Frame Up to approximately 14 days

Outcome Measure Data

Analysis Population Description
The analysis population included all participants in Part 1 who received at least one dose of study drug.
Arm/Group Title Part 1: MK-8521 64 μg/Day Part 1: MK-8521 120 μg/Day Part 1: MK-8521 34 μg/Day Part 1: MK-8521 72 μg/Day Part 1: Liraglutide 0.6 mg/Day Part 1: Liraglutide 1.2 mg/Day Part 1: Liraglutide 1.8 mg/Day Part 1: Placebo for MK-8521
Arm/Group Description Type 2 Diabetes Mellitus (T2DM) participants received once daily subcutaneous MK-8521 64 μg/day on Days 1 to 7 as part of the MK-8521 64/120 μg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 120 μg/day on Days 8 to 14 as part of the MK-8521 64/120 μg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 34 μg/day on Days 1 to 7 as part of the MK-8521 34/72 μg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 72 μg/day on Days 8 to 14 as part of the MK-8521 34/72 μg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 0.6 mg on Day 1 and 2 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 1.2 mg on Days 3 to 7 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 1.8 mg on Days 8 to 14 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days.
Measure Participants 9 7 8 8 11 11 8 8
Count of Participants [Participants]
2
20%
0
0%
0
0%
0
0%
1
5.3%
0
0%
0
0%
0
0%
4. Primary Outcome
Title Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 2
Description An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. Discontinuations are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Time Frame Up to approximately 29 days

Outcome Measure Data

Analysis Population Description
The analysis population included all participants in Part 2 who received at least one dose of study drug.
Arm/Group Title Part 2: MK-8521 64 μg/Day Part 2: MK-8521 120 μg/Day Part 2: MK-8521 180 μg/Day Part 2: MK-8521 240 μg/Day Part 2: MK-8521 300 μg/Day Part 2: Liraglutide 0.6 mg/Day Part 2: Liraglutide 1.2 mg/Day Part 2: Liraglutide 1.8 mg/Day Part 2: Placebo for MK-8521-T2DM Part 2: MK-8521 64 µg/Day-Non-Diabetic Overweight/Obese Part 2: MK-8521 120 µg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Type 2 Diabetes Mellitus (T2DM) participants received once daily subcutaneous MK-8521 64 µg/day on Days 1 to 7 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 120 µg/day on Days 8 to 14 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 180 µg/day on Days 15 to 19 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 240 µg/day on Days 20 to 24 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 300 µg/day on Days 25 to 29 as part of the MK-8521 64/120/180/240/300 µg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 0.6 mg on Days 1 to 7 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 1.2 mg on Days 8 to 14 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. Participants received once daily subcutaneous liraglutide 1.8 mg on Days 15 to 29 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 64 µg/day on Days 1 to 7 as part of the MK-8521 64/120 µg/day treatment group schedule. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 120 µg/day hon Days 8 to 14 as part of the MK-8521 64/120 µg/day treatment group schedule.
Measure Participants 18 18 18 18 15 14 13 13 6 8 8
Count of Participants [Participants]
0
0%
0
0%
0
0%
1
11.1%
0
0%
0
0%
1
16.7%
1
12.5%
1
1.1%
0
NaN
0
NaN
5. Primary Outcome
Title Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Semi-recumbent heart rate was assessed at baseline on Day 1; Day 7 at predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose; and prior to dosing on Day 8. Heart rate was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged before conducting the statistical analysis. TWA0-24hr was calculated as the area under the measurement-time curve (AUC) divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day Part 1: Liraglutide 0.6/1.2/1.8 mg/Day Part 1: Placebo for MK-8521
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days.
Measure Participants 6 8 6 8
Least Squares Mean (95% Confidence Interval) [Beats per minute]
7.19
1.17
7.42
5.69
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -0.23
Confidence Interval (2-Sided) 90%
-4.59 to 4.13
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -6.25
Confidence Interval (2-Sided) 90%
-10.48 to -2.01
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 6.02
Confidence Interval (2-Sided) 90%
1.81 to 10.22
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 1.50
Confidence Interval (2-Sided) 90%
-2.65 to 5.64
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -4.52
Confidence Interval (2-Sided) 90%
-8.52 to -0.52
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 34 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 1.73
Confidence Interval (2-Sided) 90%
-2.38 to 5.83
Parameter Dispersion Type:
Value:
Estimation Comments
6. Primary Outcome
Title Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 7 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the TWA0-24hr analysis of heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 6
Least Squares Mean (95% Confidence Interval) [Beats per minute]
1.99
4.10
-0.54
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -2.11
Confidence Interval (2-Sided) 90%
-4.55 to 0.32
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 2.53
Confidence Interval (2-Sided) 90%
-0.61 to 5.66
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 4.64
Confidence Interval (2-Sided) 90%
1.35 to 7.93
Parameter Dispersion Type:
Value:
Estimation Comments
7. Primary Outcome
Title Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 13, 14, 15, 16, 22 hours postdose and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day Part 1: Liraglutide 0.6/1.2/1.8 mg/Day Part 1: Placebo for MK-8521
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days.
Measure Participants 6 8 6 8
Least Squares Mean (95% Confidence Interval) [Beats per minute]
9.67
3.90
10.32
9.81
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -0.65
Confidence Interval (2-Sided) 90%
-5.01 to 3.71
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -6.42
Confidence Interval (2-Sided) 90%
-10.66 to -2.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 5.77
Confidence Interval (2-Sided) 90%
1.57 to 9.97
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -0.15
Confidence Interval (2-Sided) 90%
-4.29 to 4.00
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -5.91
Confidence Interval (2-Sided) 90%
-9.91 to -1.92
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 34 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 0.51
Confidence Interval (2-Sided) 90%
-3.60 to 4.62
Parameter Dispersion Type:
Value:
Estimation Comments
8. Primary Outcome
Title Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 14 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the TWA0-24hr analysis of heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
5.05
5.93
-0.20
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -0.89
Confidence Interval (2-Sided) 90%
-3.80 to 2.02
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 5.24
Confidence Interval (2-Sided) 90%
1.34 to 9.15
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 6.13
Confidence Interval (2-Sided) 90%
2.05 to 10.22
Parameter Dispersion Type:
Value:
Estimation Comments
9. Primary Outcome
Title Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 19 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, 16, hours post dose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 19 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 19 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the TWA0-24hr analysis of heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
5.62
6.20
-2.14
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -0.57
Confidence Interval (2-Sided) 90%
-3.71 to 2.57
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 7.77
Confidence Interval (2-Sided) 90%
3.50 to 12.03
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 8.34
Confidence Interval (2-Sided) 90%
3.89 to 12.79
Parameter Dispersion Type:
Value:
Estimation Comments
10. Primary Outcome
Title Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 24 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, 16, hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 24 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 24 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the TWA0-24hr analysis of heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 17 11 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
7.30
5.95
-0.99
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 1.35
Confidence Interval (2-Sided) 90%
-2.40 to 5.09
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 8.29
Confidence Interval (2-Sided) 90%
3.29 to 13.30
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 6.95
Confidence Interval (2-Sided) 90%
1.69 to 12.20
Parameter Dispersion Type:
Value:
Estimation Comments
11. Primary Outcome
Title Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 29 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent HR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose, 2, 4, 6, 8, 12, 16 and 24 hours postdose. The repeated measurements were averaged before conducting the analysis. TWA0-24hr was calculated as the AUC divided by the time period of over which the measurements were made (i.e. 24 hrs.). Change from baseline TWA0-24hr HR was calculated as the TWA0-24hr HR at Day 29 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 29 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the TWA0-24hr analysis of heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 16 11 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
8.30
5.84
-1.31
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 2.46
Confidence Interval (2-Sided) 90%
-1.42 to 6.34
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 9.61
Confidence Interval (2-Sided) 90%
4.42 to 14.81
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 7.15
Confidence Interval (2-Sided) 90%
1.70 to 12.60
Parameter Dispersion Type:
Value:
Estimation Comments
12. Primary Outcome
Title Change From Baseline in Peak Heart Rate (PHR) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 7: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 8. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 7 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of peak heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 6
Least Squares Mean (95% Confidence Interval) [Beats per minute]
7.94
11.91
8.65
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -3.97
Confidence Interval (2-Sided) 90%
-6.80 to -1.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -0.70
Confidence Interval (2-Sided) 90%
-4.33 to 2.93
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 3.26
Confidence Interval (2-Sided) 90%
-0.54 to 7.06
Parameter Dispersion Type:
Value:
Estimation Comments
13. Primary Outcome
Title Change From Baseline in Peak Heart Rate (PHR) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 14: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 15. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 14 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of peak heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 6
Least Squares Mean (95% Confidence Interval) [Beats per minute]
11.41
13.00
8.90
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -1.58
Confidence Interval (2-Sided) 90%
-5.31 to 2.15
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 2.52
Confidence Interval (2-Sided) 90%
-2.32 to 7.35
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 4.10
Confidence Interval (2-Sided) 90%
-0.96 to 9.16
Parameter Dispersion Type:
Value:
Estimation Comments
14. Primary Outcome
Title Change From Baseline in Peak Heart Rate (PHR) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 19: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 20. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 19 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 19 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of peak heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
11.26
14.75
7.30
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -3.48
Confidence Interval (2-Sided) 90%
-7.31 to 0.34
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 3.96
Confidence Interval (2-Sided) 90%
-1.11 to 9.03
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 7.44
Confidence Interval (2-Sided) 90%
2.16 to 12.73
Parameter Dispersion Type:
Value:
Estimation Comments
15. Primary Outcome
Title Change From Baseline in Peak Heart Rate (PHR) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; Day 24: predose, 2, 4, 6, 8, 12, and 16 hours postdose; and prior to dosing on Day 25. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 24 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 24 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of peak heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 17 11 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
14.09
14.06
9.39
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 0.03
Confidence Interval (2-Sided) 90%
-4.51 to 4.57
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 4.70
Confidence Interval (2-Sided) 90%
-1.33 to 10.73
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 4.66
Confidence Interval (2-Sided) 90%
-1.67 to 11.00
Parameter Dispersion Type:
Value:
Estimation Comments
16. Primary Outcome
Title Change From Baseline in Peak Heart Rate (PHR) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description PHR was defined as the maximum time matched baseline adjusted heart rate over 24 hours. Semi-recumbent PHR was measured in triplicate with at least a 1-2-minute interval between measurements at the following time points: baseline on Day 1; and Day 29: predose 2, 4, 6, 8, 12, 16, and 24 hours post dose. The repeated measurements were averaged before conducting the analysis. Change from baseline PHR was calculated as the peak heart rate at Day 29 minus baseline where baseline was defined as predose on Day 1.
Time Frame Baseline (predose Day 1) and up to 24 hours post Day 29 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of peak heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 16 11 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
16.01
12.66
7.13
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 3.34
Confidence Interval (2-Sided) 90%
-0.70 to 7.39
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 8.88
Confidence Interval (2-Sided) 90%
3.53 to 14.23
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 5.54
Confidence Interval (2-Sided) 90%
-0.08 to 11.15
Parameter Dispersion Type:
Value:
Estimation Comments
17. Primary Outcome
Title Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 7 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 7 dose (predose Day 8) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Time Frame Baseline (predose Day 1) and Day 8 (24 hours after Day 7)

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of resting morning heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 6
Least Squares Mean (95% Confidence Interval) [Beats per minute]
1.65
5.20
0.59
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -3.55
Confidence Interval (2-Sided) 90%
-6.98 to -0.12
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 1.05
Confidence Interval (2-Sided) 90%
-3.38 to 5.49
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 4.61
Confidence Interval (2-Sided) 90%
-0.02 to 9.23
Parameter Dispersion Type:
Value:
Estimation Comments
18. Primary Outcome
Title Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 14 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 14 dose (predose Day 15) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Time Frame Baseline (predose Day 1) and Day 15 (24 hours after Day 14)

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of resting morning heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
4.22
5.38
-4.42
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -1.16
Confidence Interval (2-Sided) 90%
-4.59 to 2.28
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 8.65
Confidence Interval (2-Sided) 90%
3.99 to 13.31
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 9.80
Confidence Interval (2-Sided) 90%
4.96 to 14.65
Parameter Dispersion Type:
Value:
Estimation Comments
19. Primary Outcome
Title Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 19 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 19 dose (predose Day 20) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Time Frame Baseline (predose Day 1) and Day 20 (24 hours after Day 19)

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of resting morning heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 12 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
6.41
10.44
-3.82
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -4.04
Confidence Interval (2-Sided) 90%
-7.52 to -0.56
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 10.23
Confidence Interval (2-Sided) 90%
5.57 to 14.89
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 14.27
Confidence Interval (2-Sided) 90%
9.38 to 19.15
Parameter Dispersion Type:
Value:
Estimation Comments
20. Primary Outcome
Title Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 24 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 24 dose (predose Day 25) minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Time Frame Baseline (predose Day 1) and Day 25 (24 hours after Day 24)

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of resting morning heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 16 11 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
7.51
9.63
-5.82
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -2.12
Confidence Interval (2-Sided) 90%
-5.70 to 1.47
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 13.34
Confidence Interval (2-Sided) 90%
8.64 to 18.03
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 15.45
Confidence Interval (2-Sided) 90%
10.53 to 20.38
Parameter Dispersion Type:
Value:
Estimation Comments
21. Primary Outcome
Title Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 29 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description Semi-recumbent RMHR was measured in triplicate with at least a 1-2-minute interval between measurements. The repeated measurements were averaged for each time point. Change from baseline RMHR was calculated as the RMHR 24 hours after the Day 29 dose minus baseline. Baseline was an average of 2 readings prior to dosing on Day 1.
Time Frame Baseline (predose Day 1) and Day 30 (24 hours after Day 29)

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. Per-protocol, non-diabetic overweight/obese participants were not planned for the analysis of resting morning heart rate.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 16 11 5
Least Squares Mean (95% Confidence Interval) [Beats per minute]
9.41
7.30
-1.02
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 2.11
Confidence Interval (2-Sided) 90%
-1.47 to 5.70
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 10.43
Confidence Interval (2-Sided) 90%
5.73 to 15.13
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 8.32
Confidence Interval (2-Sided) 90%
3.40 to 13.24
Parameter Dispersion Type:
Value:
Estimation Comments
22. Primary Outcome
Title Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1, 7, and 14

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 9 8
Day 1
6.11
(47.6)
2.25
(27.5)
Day 7
14.4
(55.9)
5.63
(24.6)
Day 14
32.8
(42.8)
12.6
(26.6)
23. Primary Outcome
Title Maximum Concentration (Cmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Cmax was the maximum observed concentration of MK-8521 in plasma after administration. Plasma samples were collected from predose to 24 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 9 8
Day 1
0.350
(41.4)
0.128
(21.4)
Day 7
0.710
(57.6)
0.275
(31.2)
24. Primary Outcome
Title Maximum Concentration (Cmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Cmax was the maximum observed concentration of MK-8521 in plasma after administration on Day 14. Plasma samples were collected from predose to 120 hours postdose for determination of Cmax. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 7 8
Geometric Mean (Geometric Coefficient of Variation) [nM]
1.70
(38.4)
0.619
(27.0)
25. Primary Outcome
Title Trough Concentration (Ctrough) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Ctrough was the lowest observed concentration of MK-8521 in plasma. Plasma samples were collected predose on Day 2 (sampled after the Day 1 dose and prior to Day 2 dose), 7, and 14 for determination of Ctrough. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Ctrough is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose on Days 2, 7, and 14

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 9 8
Day 1
0.322
(33.2)
0.119
(20.6)
Day 7
0.442
(83.6)
0.207
(21.8)
Day 14
1.16
(43.3)
0.506
(27.5)
26. Primary Outcome
Title Time to Maximum Concentration (Tmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 24 hours postdose for determination of Tmax. Tmax is presented as median with a full range.
Time Frame Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 9 8
Day 1
16
16
Day 7
7
6
27. Primary Outcome
Title Time to Maximum Concentration (Tmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 120 hours postdose for determination of Tmax. Tmax is presented as median with a full range.
Time Frame Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 7 8
Median (Full Range) [Hours]
8
6
28. Primary Outcome
Title Apparent Terminal Half Life (t1/2) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 24 hours postdose for determination of t1/2. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint. t1/2 was not measured for Days 1 and 7 since terminal phase was not adequately captured with sampling times up to 24 hours post dose.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 0 0
29. Primary Outcome
Title Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 120 hours postdose for determination of t1/2. t1/2 was measured on Day 14 which is the longest time point for sampling for T2DM participants in Part 1. t1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 7 8
Geometric Mean (Geometric Coefficient of Variation) [Hours]
15.6
(16.1)
17.2
(17.0)
30. Primary Outcome
Title Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio with a full range.
Time Frame Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 7 8
Geometric Mean (Full Range) [Ratio]
2.31
2.50
31. Primary Outcome
Title Accumulation Ratio of the Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of Cmax. The geometric mean accumulation ratio was calculated as Day 7 Cmax/Day 1 Cmax and presented as geometric mean ratio with a full range.
Time Frame Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 7 8
Geometric Mean (Full Range) [Ratio]
2.00
2.14
32. Primary Outcome
Title Accumulation Ratio of the Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description Plasma samples were collected predose on Days 2 (sampled after the Day 1 dose and prior to Day 2 dose) and 7 for determination of the accumulation ratio of Ctrough. The geometric mean accumulation ratio was calculated as Day 7 Ctrough/Day 1 Ctrough (sampled after the Day 1 dose and prior to Day 2 dose) and presented as geometric mean ratio with a full range.
Time Frame Predose on Days 2 and 7

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14.
Measure Participants 7 8
Geometric Mean (Full Range) [Ratio]
1.37
1.73
33. Primary Outcome
Title Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Description AUC0-24hr was the area under the concentration-time curve of MK-8521 from time zero to 24 hours after administration. Plasma samples were collected from predose to 24 hours postdose for determination of AUC0-24hr. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. AUC0-24hr is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose and 1, 2, 6, 10, 16, and 24 hours postdose on Days 1, 7, and 14

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: MK-8521 64/120 µg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 µg starting at 64 µg and increasing to 120 µg on Day 8. The total number of dosing days was 14.
Measure Participants 18 8
Day 1
6.46
(49.5)
7.68
(34.8)
Day 7
15.1
(35.6)
15.0
(35.9)
Day 14
30.0
(35.8)
34.4
(19.5)
34. Primary Outcome
Title Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Description Plasma samples were collected from predose to 24 hours postdose for determination of the accumulation ratio of AUC0-24hr. The geometric mean accumulation ratio was calculated as Day 7 AUC0-24hr/Day 1 AUC0-24hr and presented as geometric mean ratio and percent geometric coefficient of variation.
Time Frame Predose and 1, 2, 6, 10, 16, and 24 hours post-dose on Days 1 and 7

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: MK-8521 64/120 µg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 µg starting at 64 µg and increasing to 120 µg on Day 8. The total number of dosing days was 14.
Measure Participants 18 8
Geometric Mean (Geometric Coefficient of Variation) [Ratio]
2.33
(22.2)
1.95
(28.6)
35. Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description FPG was measured predose on Days 1 and 7. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 7. FPG is presented as mean change from baseline with a standard error.
Time Frame Predose on Days 1 (baseline) and 7

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day Part 1: Liraglutide 0.6/1.2/1.8 mg/Day Part 1: Placebo for MK-8521
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. Participants received once daily subcutaneous placebo for MK-8521 for 14 days.
Measure Participants 7 8 9 8
Mean (Standard Error) [mg/dL]
-23.57
(10.75)
-39.00
(8.44)
-59.11
(7.09)
-11.13
(7.26)
36. Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description FPG was measured predose on Days 1 and 14. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 14. FPG is presented as mean change from baseline with a standard error.
Time Frame Predose on Days 1 (baseline) and 14

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day Part 1: Liraglutide 0.6/1.2/1.8 mg/Day Part 1: Placebo for MK-8521
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. Participants received once daily subcutaneous placebo for MK-8521 for 14 days.
Measure Participants 7 8 8 8
Mean (Standard Error) [mg/dL]
-41.29
(11.22)
-48.50
(13.21)
-59.25
(4.98)
-13.50
(9.54)
37. Secondary Outcome
Title Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Blood samples for glucose were collected immediately prior to, and after each meal. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Blood for plasma glucose concentrations was obtained at predose Day 1 at pre meal (breakfast), 0.5, 1, 2, 3, 4 (pre lunch), 4.5, 5, 6, 7, 10 (pre dinner), 10.5, 11, 12, 13, 15 and 23 hours post breakfast meal; and on Day 7 at 1 (pre breakfast), 1.5, 2, 3, 4, 5 (pre lunch), 5.5, 6, 7, 8, 11 (pre dinner), 11.5, 12, 13, 14, 16, 24 hours post dose. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with fixed effects for treatment, day and treatment by day interaction, a random effect for participant, and baseline 24-hour WMG as a covariate. WMG is presented as least squares mean with a 95% confidence interval.
Time Frame Baseline (predose and before food on Day 1) and up to 24 hours post Day 7 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day Part 1: Liraglutide 0.6/1.2/1.8 mg/Day Part 1: Placebo for MK-8521
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. Participants received once daily subcutaneous placebo for MK-8521 for 14 days.
Measure Participants 6 8 6 8
Least Squares Mean (95% Confidence Interval) [mg/dL]
-24.08
-27.54
-53.64
2.36
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 29.56
Confidence Interval (2-Sided) 90%
4.34 to 54.77
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 26.10
Confidence Interval (2-Sided) 90%
2.02 to 50.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 3.45
Confidence Interval (2-Sided) 90%
-20.23 to 27.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -26.45
Confidence Interval (2-Sided) 90%
-49.96 to -2.93
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -29.90
Confidence Interval (2-Sided) 90%
-52.04 to -7.77
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 34 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -56.00
Confidence Interval (2-Sided) 90%
-79.53 to -32.48
Parameter Dispersion Type:
Value:
Estimation Comments
38. Secondary Outcome
Title Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1
Description The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Blood samples for glucose were collected immediately prior to and after each meal. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Blood for plasma glucose concentrations was obtained on Day -1 at pre meal (breakfast), 0.5, 1, 2, 3, 4 (pre lunch), 4.5, 5, 6, 7, 10 (pre dinner), 10.5, 11, 12, 13, 15 and 23 hours post breakfast meal; and on Day 14 at 1 (pre breakfast), 1.5, 2, 3, 4, 5 (pre lunch), 5.5, 6, 7, 8, 11(pre dinner), 11.5, 12, 13, 14, 16, 24 hours post dose. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with fixed effects for treatment, day and treatment by day interaction, a random effect for participant, and baseline 24-hour WMG as a covariate. WMG is presented as least squares mean with a 95% confidence interval.
Time Frame Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 1: MK-8521 64/120 μg/Day Part 1: MK-8521 34/72 μg/Day Part 1: Liraglutide 0.6/1.2/1.8 mg/Day Part 1: Placebo for MK-8521
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 starting at 64 μg on Days 1 to 7 and escalated to 120 μg on Days 8 to 14. T2DM participants received once daily subcutaneous MK-8521 starting at 34 μg on Days 1 to 7 and escalated to 72 μg on Days 8 to 14. T2DM participants received once daily subcutaneous liraglutide starting at 0.6 mg on Day 1 and 2, escalated to 1.2 mg on Days 3 to 7, and escalated to 1.8 mg on Days 8 to 14. Participants received once daily subcutaneous placebo for MK-8521 for 14 days.
Measure Participants 6 8 6 8
Least Squares Mean (95% Confidence Interval) [mg/dL]
-37.24
-45.63
-52.20
-2.00
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 14.96
Confidence Interval (2-Sided) 90%
-10.25 to 40.18
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 6.57
Confidence Interval (2-Sided) 90%
-17.52 to 30.65
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 8.40
Confidence Interval (2-Sided) 90%
-15.29 to 32.08
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -35.23
Confidence Interval (2-Sided) 90%
-58.75 to -11.72
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -43.63
Confidence Interval (2-Sided) 90%
-65.77 to -21.50
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 34 μg/Day, Part 1: MK-8521 72 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -50.20
Confidence Interval (2-Sided) 90%
-73.72 to -26.68
Parameter Dispersion Type:
Value:
Estimation Comments
39. Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description FPG was measured predose on Days 1 and 14. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 14. FPG is presented as least squares mean change from baseline with a 95% confidence interval.
Time Frame Predose on Days 1 (baseline) and 14

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 5
Least Squares Mean (95% Confidence Interval) [mg/dL]
-45.89
-39.80
-14.69
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -31.20
Confidence Interval (2-Sided) 90%
-56.59 to -5.81
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -25.12
Confidence Interval (2-Sided) 90%
-50.25 to 0.01
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -6.08
Confidence Interval (2-Sided) 90%
-17.31 to 5.14
Parameter Dispersion Type:
Value:
Estimation Comments
40. Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description FPG was measured predose on Days 1 and 19. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 19. FPG is presented as least squares mean change from baseline with a 95% confidence interval.
Time Frame Predose on Days 1 (baseline) and 19

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 5
Least Squares Mean (95% Confidence Interval) [mg/dL]
-44.22
-47.33
-16.74
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -27.48
Confidence Interval (2-Sided) 90%
-52.87 to -2.09
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -30.59
Confidence Interval (2-Sided) 90%
-55.72 to -5.46
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 3.11
Confidence Interval (2-Sided) 90%
-8.11 to 14.34
Parameter Dispersion Type:
Value:
Estimation Comments
41. Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description FPG was measured predose on Days 1 and 24. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 24. FPG is presented as least squares mean change from baseline with a 95% confidence interval.
Time Frame Predose on Days 1 (baseline) and 24

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 17 11 5
Least Squares Mean (95% Confidence Interval) [mg/dL]
-40.14
-50.14
-44.73
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 4.59
Confidence Interval (2-Sided) 90%
-20.88 to 30.06
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -5.42
Confidence Interval (2-Sided) 90%
-30.68 to 19.85
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 10.01
Confidence Interval (2-Sided) 90%
-1.77 to 21.78
Parameter Dispersion Type:
Value:
Estimation Comments
42. Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description FPG was measured predose on Days 1 and 29. The change from baseline of FPG was calculated as the difference between the predose measurement on Day 1 (baseline) and the measurement obtained predose on Day 29. FPG is presented as least squares mean change from baseline with a 95% confidence interval.
Time Frame Predose on Days 1 (baseline) and 29

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 16 11 5
Least Squares Mean (95% Confidence Interval) [mg/dL]
-52.54
-52.06
-37.55
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -14.98
Confidence Interval (2-Sided) 90%
-40.53 to 10.57
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -14.50
Confidence Interval (2-Sided) 90%
-39.77 to 10.76
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -0.48
Confidence Interval (2-Sided) 90%
-12.47 to 11.52
Parameter Dispersion Type:
Value:
Estimation Comments
43. Secondary Outcome
Title Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 14 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 14 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.
Time Frame Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 5
Least Squares Mean (95% Confidence Interval) [mg/dL]
-47.52
-51.24
-3.84
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -43.68
Confidence Interval (2-Sided) 90%
-65.81 to -21.55
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -47.40
Confidence Interval (2-Sided) 90%
-69.35 to -25.45
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 3.72
Confidence Interval (2-Sided) 90%
-5.76 to 13.19
Parameter Dispersion Type:
Value:
Estimation Comments
44. Secondary Outcome
Title Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 19 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 19 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.
Time Frame Baseline (predose and before food on Day 1) and up to 24 hours post Day 19 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 18 13 5
Least Squares Mean (95% Confidence Interval) [mg/dL]
-52.23
-57.43
-18.22
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -34.01
Confidence Interval (2-Sided) 90%
-56.14 to -11.88
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -39.20
Confidence Interval (2-Sided) 90%
-61.15 to -17.26
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 5.20
Confidence Interval (2-Sided) 90%
-4.28 to 14.67
Parameter Dispersion Type:
Value:
Estimation Comments
45. Secondary Outcome
Title Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 24 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 24 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.
Time Frame Baseline (predose and before food on Day 1) and up to 24 hours post Day 24 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 16 11 5
Least Squares Mean (95% Confidence Interval) [mg/dL]
-50.44
-60.66
-26.71
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -23.73
Confidence Interval (2-Sided) 90%
-45.89 to -1.56
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -33.95
Confidence Interval (2-Sided) 90%
-55.93 to -11.98
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 10.23
Confidence Interval (2-Sided) 90%
0.56 to 19.89
Parameter Dispersion Type:
Value:
Estimation Comments
46. Secondary Outcome
Title Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC0-24hr) divided by 24 hours. Plasma glucose concentrations were obtained on Day -1 at pre meal (breakfast), 1, 3, 4 (pre lunch), 5, 7, 10 (pre dinner), 11, 13, 15 and 23 hours post breakfast meal and Day 29 at 1 (pre breakfast), 2, 4, 5 (pre lunch), 6, 8, 11 (pre dinner), 12, 14, 16, 24 hours post dose. The timing of samples on Day -1 are relative to the breakfast meal. Day 29 samples are relative to dosing. The change from baseline value for 24-hour WMG was calculated where baseline was the WMG before food and prior to treatment on Day 1. Individual change from baseline 24-hour WMG was analyzed in a linear mixed effects model with group, day and group by day interaction as fixed effects, baseline 24-hour WMG as a covariate, and participant as a random effect. WMG is presented as least squares mean with a 95% confidence interval.
Time Frame Baseline (predose and before food on Day 1) and up to 24 hours post Day 29 dose

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM Part 2: Placebo for MK-8521-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 µg starting at 64 µg and increasing to 120 µg on Day 8, 180 µg on Day 15, 240 µg on Day 20, and 300 µg on Day 25. The total number of dosing days was 29. T2DM participants received once daily subcutaneous liraglutide titrated to 1.8 mg starting at 0.6 mg and increasing to 1.2 mg on Day 8, and 1.8 mg on Day 15. The total number of dosing days was 29. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days.
Measure Participants 16 11 5
Least Squares Mean (95% Confidence Interval) [mg/dL]
-53.44
-59.72
-29.96
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -23.49
Confidence Interval (2-Sided) 90%
-45.65 to -1.32
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 120 μg/Day, Part 1: MK-8521 34 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value -29.76
Confidence Interval (2-Sided) 90%
-51.74 to -7.79
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Part 1: MK-8521 64 μg/Day, Part 1: MK-8521 120 μg/Day
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference of Least Squares Means
Estimated Value 6.27
Confidence Interval (2-Sided) 90%
-3.39 to 15.93
Parameter Dispersion Type:
Value:
Estimation Comments
47. Secondary Outcome
Title Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Description Cmax was the maximum observed concentration of MK-8521 in plasma after administration. Plasma samples were collected from predose to 120 hours postdose for determination of Cmax. Per protocol, Cmax in the non-diabetic overweight/obese participants was not measured on Days 19, 24, and 29 because they only received 14 days of treatment. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Cmax is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose and 1, 2, 6, 10, 16, 24 hours post dose on Days 1, 7, 14, 19, 24 (T2DM) and Days 1 and 7 (Non-Diabetic Overweight/Obese); predose and 1, 2, 6, 10, 16, 24, 72, 96. and 120 hours post dose on Day 14 (Non-Diabetic Overweight/Obese) and Day 29 (T2DM).

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 μg/Day-T2DM Part 2: MK-8521 64/120 μg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 μg starting at 64 μg and increasing to 120 μg on Day 8, 180 μg on Day 15, 240 μg on Day 20, and 300 μg on Day 25. The total number of dosing days was 29. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 μg starting at 64 μg and increasing to 120 μg on Day 8. The total number of dosing days was 14.
Measure Participants 18 8
Day 1
0.35
(48.0)
0.411
(32.1)
Day 7
0.719
(34.6)
0.742
(38.7)
Day 14
1.43
(35.8)
1.72
(20.0)
Day 19
2.27
(38.6)
Day 24
2.85
(33.1)
Day 29
3.14
(34.1)
48. Secondary Outcome
Title Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Description Ctrough was the lowest observed concentration of MK-8521 in plasma. Plasma samples were collected predose on Day 2 (sampled after the Day 1 dose and prior to Day 2 dose), 7, 14, 19, 24, and 29 for determination of Ctrough. Per protocol, Ctrough in the non-diabetic overweight/obese participants was not measured on Days 19, 24, and 29 because they only received 14 days of treatment. Individual values were natural log-transformed and evaluated with a linear-mixed effects model containing fixed effects for treatment, day, and treatment by day interaction, and a random effect for participant. Kenward and Roger's method was used to calculate the degree of freedom for the fixed effects. Ctrough is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose on Days 2 (sampled 24 hours after Day 1 dose) and 7, 14, 19, 24, and 29

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 μg/Day-T2DM Part 2: MK-8521 64/120 μg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 μg starting at 64 μg and increasing to 120 μg on Day 8, 180 μg on Day 15, 240 μg on Day 20, and 300 μg on Day 25. The total number of dosing days was 29. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 μg starting at 64 μg and increasing to 120 μg on Day 8. The total number of dosing days was 14.
Measure Participants 18 8
Day 1
0.331
(45.5)
0.388
(32.8)
Day 7
0.533
(32.7)
0.492
(29.1)
Day 14
1.07
(36.0)
1.12
(21.8)
Day 19
1.61
(33.8)
Day 24
2.02
(30.6)
Day 29
2.47
(29.9)
49. Secondary Outcome
Title Time to Maximum Concentration (Tmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2
Description Tmax was the time required to reach the maximum concentration of MK-8521 in plasma. Plasma samples were collected from predose to 120 hours postdose for determination of Tmax. Per protocol, Tmax in the non-diabetic overweight/obese participants was not measured on Days 19, 24, and 29 because they only received 14 days of treatment. Tmax is presented as median with a full range.
Time Frame Predose and 1, 2, 6, 10, 16, 24 hours post dose on Days 1, 7, 14, 19, 24 (T2DM) and Days 1 and 7 (Non-Diabetic Overweight/Obese); predose and 1, 2, 6, 10, 16, 24, 72, 96. and 120 hours post dose on Day 14 (Non-Diabetic Overweight/Obese) and Day 29 (T2DM).

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 μg/Day-T2DM Part 2: MK-8521 64/120 μg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 μg starting at 64 μg and increasing to 120 μg on Day 8, 180 μg on Day 15, 240 μg on Day 20, and 300 μg on Day 25. The total number of dosing days was 29. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 μg starting at 64 μg and increasing to 120 μg on Day 8. The total number of dosing days was 14.
Measure Participants 18 8
Day 1
16
16
Day 7
10
10
Day 14
6
6
Day 19
6
Day 24
6
Day 29
10
50. Secondary Outcome
Title Apparent Terminal Half Life (t1/2) of MK-8521 on Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2
Description t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 120 hours postdose for determination of t1/2. Per protocol, t1/2 was measured on Day 29 which is the longest time point for sampling for T2DM participants 1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose and 1, 2, 6, 10, 16, 24, 72, 96 and 120 hours post dose on Day 29

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120/180/240/300 μg/Day-T2DM
Arm/Group Description Type 2 diabetes mellitus (T2DM) participants received once daily subcutaneous MK-8521 titrated to 300 μg starting at 64 μg and increasing to 120 μg on Day 8, 180 μg on Day 15, 240 μg on Day 20, and 300 μg on Day 25. The total number of dosing days was 29.
Measure Participants 16
Geometric Mean (Geometric Coefficient of Variation) [Hours]
15.4
(10.2)
51. Secondary Outcome
Title Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Non-Diabetic Overweight/Obese Participants in Part 2
Description t1/2 was the time required to divide the MK-8521 concentration by half after reaching pseudo-equilibrium. Plasma samples were collected from predose to 24 hours postdose for determination of t1/2. Per protocol, t1/2 was measured on Day 14 which is the longest time point for sampling for non-diabetic overweight/obese participants 1/2 is presented as geometric mean and percent coefficient of variation of geometric mean.
Time Frame Predose and 1, 2, 6, 10, 16, and 24 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description
The analysis population included a subset of participants who complied with the protocol sufficiently to ensure that their data exhibited the effects of treatment according to the underlying scientific model and had data available for the analysis of the endpoint.
Arm/Group Title Part 2: MK-8521 64/120 μg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 titrated to 120 μg starting at 64 μg and increasing to 120 μg on Day 8. The total number of dosing days was 14.
Measure Participants 8
Geometric Mean (Geometric Coefficient of Variation) [Hours]
14.4
(10.8)

Adverse Events

Time Frame Up to approximately 42 days for Part 1 and up to approximately 57 days for Part 2
Adverse Event Reporting Description All participants that received ≥1 dose of study drug for adverse events (AEs) and all randomized participants for all-cause mortality. AEs and all-cause mortality are presented by individual dose received by participants during titration in an assigned study treatment sequence.
Arm/Group Title Part 1: MK-8521 64 μg/Day Part 1: MK-8521 120 μg/Day Part 1: MK-8521 34 μg/Day Part 1: MK-8521 72 μg/Day Part 1: Liraglutide 0.6 mg/Day Part 1: Liraglutide 1.2 mg/Day Part 1: Liraglutide 1.8 mg/Day Part 1: Placebo for MK-8521 Part 2: MK-8521 64 μg/Day T2DM Part 2: MK-8521 120 μg/Day T2DM Part 2: MK-8521 180 μg/Day T2DM Part 2: MK-8521 240 μg/Day T2DM Part 2: MK-8521 300 μg/Day T2DM Part 2: Liraglutide 0.6 mg/Day T2DM Part 2: Liraglutide 1.2 mg/Day T2DM Part 2: Liraglutide 1.8 mg/Day T2DM Part 2: Placebo for MK-8521-T2DM Part 2: MK-8521 64 μg/Day-Non-Diabetic Overweight/Obese Part 2: MK-8521 120 μg/Day-Non-Diabetic Overweight/Obese
Arm/Group Description Type 2 Diabetes Mellitus (T2DM) participants received once daily subcutaneous MK-8521 64 μg/day on Days 1 to 7 as part of the MK-8521 64/120 μg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 120 μg/day on Days 8 to 14 as part of the MK-8521 64/120 μg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 34 μg/day on Days 1 to 7 as part of the MK-8521 34/72 μg/day treatment group schedule. T2DM participants received once daily subcutaneous MK-8521 72 μg/day on Days 8 to 14 as part of the MK-8521 34/72 μg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 0.6 mg on Day 1 and 2 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 1.2 mg on Days 3 to 7 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous liraglutide 1.8 mg on Days 8 to 14 as part of the liraglutide 0.6/1.2/1.8 mg/day treatment group schedule. T2DM participants received once daily subcutaneous placebo for MK-8521 for 14 days. Type 2 Diabetes Mellitus (T2DM) participants received once daily subcutaneous MK-8521 64 µg on Days 1 to 7 as part of the MK-8521 64/120/180/240/300 µg treatment sequence. T2DM participants received once daily subcutaneous MK-8521 120 µg on Days 8 to 14 as part of the MK-8521 64/120/180/240/300 µg treatment sequence. T2DM participants received once daily subcutaneous MK-8521 180 µg on Days 15 to 19 as part of the MK-8521 64/120/180/240/300 µg treatment sequence. T2DM participants received once daily subcutaneous MK-8521 240 µg on Days 20 to 24 as part of the MK-8521 64/120/180/240/300 µg treatment sequence. T2DM participants received once daily subcutaneous MK-8521 300 µg on Days 25 to 29 as part of the MK-8521 64/120/180/240/300 µg treatment sequence. T2DM participants received once daily subcutaneous liraglutide 0.6 mg on Days 1 to 7 as part of the liraglutide 0.6/1.2/1.8 mg treatment sequence. T2DM participants received once daily subcutaneous liraglutide 1.2 mg on Days 8 to 14 as part of the liraglutide 0.6/1.2/1.8 mg treatment sequence. T2DM participants received once daily subcutaneous liraglutide 1.8 mg on Days 15 to 29 as part of the liraglutide 0.6/1.2/1.8 mg treatment sequence. T2DM participants received once daily subcutaneous placebo for MK-8521 for 29 days. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 64 µg on Days 1 to 7 as part of the MK-8521 64/120 µg treatment sequence. Non-diabetic overweight/obese participants received once daily subcutaneous MK-8521 120 µg on Days 8 to 14 as part of the MK-8521 64/120 µg treatment sequence.
All Cause Mortality
Part 1: MK-8521 64 μg/Day Part 1: MK-8521 120 μg/Day Part 1: MK-8521 34 μg/Day Part 1: MK-8521 72 μg/Day Part 1: Liraglutide 0.6 mg/Day Part 1: Liraglutide 1.2 mg/Day Part 1: Liraglutide 1.8 mg/Day Part 1: Placebo for MK-8521 Part 2: MK-8521 64 μg/Day T2DM Part 2: MK-8521 120 μg/Day T2DM Part 2: MK-8521 180 μg/Day T2DM Part 2: MK-8521 240 μg/Day T2DM Part 2: MK-8521 300 μg/Day T2DM Part 2: Liraglutide 0.6 mg/Day T2DM Part 2: Liraglutide 1.2 mg/Day T2DM Part 2: Liraglutide 1.8 mg/Day T2DM Part 2: Placebo for MK-8521-T2DM Part 2: MK-8521 64 μg/Day-Non-Diabetic Overweight/Obese Part 2: MK-8521 120 μg/Day-Non-Diabetic Overweight/Obese
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/10 (0%) 0/7 (0%) 0/8 (0%) 0/8 (0%) 0/11 (0%) 0/11 (0%) 0/8 (0%) 0/8 (0%) 0/18 (0%) 0/18 (0%) 0/18 (0%) 0/18 (0%) 0/15 (0%) 0/14 (0%) 0/13 (0%) 0/13 (0%) 0/6 (0%) 0/8 (0%) 0/8 (0%)
Serious Adverse Events
Part 1: MK-8521 64 μg/Day Part 1: MK-8521 120 μg/Day Part 1: MK-8521 34 μg/Day Part 1: MK-8521 72 μg/Day Part 1: Liraglutide 0.6 mg/Day Part 1: Liraglutide 1.2 mg/Day Part 1: Liraglutide 1.8 mg/Day Part 1: Placebo for MK-8521 Part 2: MK-8521 64 μg/Day T2DM Part 2: MK-8521 120 μg/Day T2DM Part 2: MK-8521 180 μg/Day T2DM Part 2: MK-8521 240 μg/Day T2DM Part 2: MK-8521 300 μg/Day T2DM Part 2: Liraglutide 0.6 mg/Day T2DM Part 2: Liraglutide 1.2 mg/Day T2DM Part 2: Liraglutide 1.8 mg/Day T2DM Part 2: Placebo for MK-8521-T2DM Part 2: MK-8521 64 μg/Day-Non-Diabetic Overweight/Obese Part 2: MK-8521 120 μg/Day-Non-Diabetic Overweight/Obese
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/9 (11.1%) 0/7 (0%) 0/8 (0%) 0/8 (0%) 0/11 (0%) 0/11 (0%) 0/8 (0%) 0/8 (0%) 0/18 (0%) 0/18 (0%) 0/18 (0%) 1/18 (5.6%) 0/15 (0%) 0/14 (0%) 0/13 (0%) 0/13 (0%) 0/6 (0%) 0/8 (0%) 0/8 (0%)
Cardiac disorders
Sick sinus syndrome 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Supraventricular tachycardia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Nervous system disorders
Convulsion 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Presyncope 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Other (Not Including Serious) Adverse Events
Part 1: MK-8521 64 μg/Day Part 1: MK-8521 120 μg/Day Part 1: MK-8521 34 μg/Day Part 1: MK-8521 72 μg/Day Part 1: Liraglutide 0.6 mg/Day Part 1: Liraglutide 1.2 mg/Day Part 1: Liraglutide 1.8 mg/Day Part 1: Placebo for MK-8521 Part 2: MK-8521 64 μg/Day T2DM Part 2: MK-8521 120 μg/Day T2DM Part 2: MK-8521 180 μg/Day T2DM Part 2: MK-8521 240 μg/Day T2DM Part 2: MK-8521 300 μg/Day T2DM Part 2: Liraglutide 0.6 mg/Day T2DM Part 2: Liraglutide 1.2 mg/Day T2DM Part 2: Liraglutide 1.8 mg/Day T2DM Part 2: Placebo for MK-8521-T2DM Part 2: MK-8521 64 μg/Day-Non-Diabetic Overweight/Obese Part 2: MK-8521 120 μg/Day-Non-Diabetic Overweight/Obese
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 5/9 (55.6%) 5/7 (71.4%) 1/8 (12.5%) 4/8 (50%) 2/11 (18.2%) 7/11 (63.6%) 2/8 (25%) 5/8 (62.5%) 8/18 (44.4%) 14/18 (77.8%) 6/18 (33.3%) 13/18 (72.2%) 8/15 (53.3%) 8/14 (57.1%) 8/13 (61.5%) 12/13 (92.3%) 3/6 (50%) 2/8 (25%) 4/8 (50%)
Cardiac disorders
Palpitations 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Sinus tachycardia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Supraventricular tachycardia 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 2 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Tachycardia 2/9 (22.2%) 2 1/7 (14.3%) 1 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Tachycardia paroxysmal 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Ventricular extrasystoles 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Ventricular tachycardia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Ear and labyrinth disorders
Ear pain 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 2/13 (15.4%) 2 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Eye disorders
Vision blurred 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Gastrointestinal disorders
Abdominal discomfort 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Abdominal distension 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 1/18 (5.6%) 1 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Abdominal pain 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 2 0/8 (0%) 0 0/8 (0%) 0 2/18 (11.1%) 2 2/18 (11.1%) 2 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 1/13 (7.7%) 1 2/13 (15.4%) 2 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Abdominal pain upper 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 1/15 (6.7%) 1 1/14 (7.1%) 1 0/13 (0%) 0 3/13 (23.1%) 4 0/6 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1
Aphthous stomatitis 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Change of bowel habit 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 1/14 (7.1%) 1 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1
Constipation 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 4/18 (22.2%) 4 1/18 (5.6%) 1 0/18 (0%) 0 0/15 (0%) 0 1/14 (7.1%) 1 1/13 (7.7%) 1 2/13 (15.4%) 3 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Diarrhoea 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/11 (27.3%) 3 0/8 (0%) 0 0/8 (0%) 0 4/18 (22.2%) 6 6/18 (33.3%) 6 0/18 (0%) 0 1/18 (5.6%) 1 3/15 (20%) 3 5/14 (35.7%) 6 0/13 (0%) 0 4/13 (30.8%) 4 1/6 (16.7%) 1 1/8 (12.5%) 1 0/8 (0%) 0
Dry mouth 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Dyspepsia 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 3/11 (27.3%) 3 0/8 (0%) 0 1/8 (12.5%) 1 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 2/18 (11.1%) 2 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Flatulence 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Gingival pain 0/9 (0%) 0 1/7 (14.3%) 1 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Haematochezia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Haemorrhoids 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 1/14 (7.1%) 1 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Mouth ulceration 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Nausea 0/9 (0%) 0 1/7 (14.3%) 1 0/8 (0%) 0 1/8 (12.5%) 1 1/11 (9.1%) 1 4/11 (36.4%) 4 0/8 (0%) 0 0/8 (0%) 0 2/18 (11.1%) 4 4/18 (22.2%) 4 0/18 (0%) 0 5/18 (27.8%) 6 1/15 (6.7%) 1 5/14 (35.7%) 7 2/13 (15.4%) 3 5/13 (38.5%) 6 1/6 (16.7%) 1 0/8 (0%) 0 1/8 (12.5%) 1
Regurgitation 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Retching 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 1/14 (7.1%) 1 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Toothache 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Vomiting 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 3 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 2 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 1/14 (7.1%) 1 0/13 (0%) 0 2/13 (15.4%) 3 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
General disorders
Application site dermatitis 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 1/14 (7.1%) 1 0/13 (0%) 0 1/13 (7.7%) 2 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Application site erythema 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Application site irritation 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/8 (12.5%) 1 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 1/6 (16.7%) 1 0/8 (0%) 0 1/8 (12.5%) 1
Application site pruritus 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Asthenia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Catheter site erythema 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Catheter site haemorrhage 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 1/13 (7.7%) 1 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Catheter site oedema 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Chest pain 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Early satiety 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Feeling cold 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Feeling hot 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Influenza like illness 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Injection site erythema 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Injection site haemorrhage 0/9 (0%) 0 1/7 (14.3%) 1 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Injection site injury 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Injection site macule 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Oedema peripheral 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Peripheral swelling 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Pyrexia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Vessel puncture site erythema 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Vessel puncture site haemorrhage 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Vessel puncture site pain 0/9 (0%) 0 0/7 (0%) 0 1/8 (12.5%) 1 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Xerosis 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Infections and infestations
Hordeolum 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Localised infection 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Tooth infection 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Urinary tract infection 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Viral infection 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Viral pharyngitis 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Injury, poisoning and procedural complications
Post-traumatic pain 0/9 (0%) 0 1/7 (14.3%) 1 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Skin abrasion 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 2/13 (15.4%) 3 0/6 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1
Investigations
Lipase increased 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 0/18 (0%) 0 4/18 (22.2%) 4 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Weight decreased 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Metabolism and nutrition disorders
Decreased appetite 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 2/18 (11.1%) 2 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 2/14 (14.3%) 2 1/13 (7.7%) 1 0/13 (0%) 0 1/6 (16.7%) 1 1/8 (12.5%) 1 0/8 (0%) 0
Hyperglycaemia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Hypertriglyceridaemia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Hypoglycaemia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Increased appetite 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Musculoskeletal and connective tissue disorders
Back pain 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 2/18 (11.1%) 2 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Muscle spasms 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Musculoskeletal chest pain 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Neck pain 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Pain in extremity 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Nervous system disorders
Dizziness 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 1/18 (5.6%) 1 1/18 (5.6%) 1 0/18 (0%) 0 0/15 (0%) 0 1/14 (7.1%) 2 0/13 (0%) 0 1/13 (7.7%) 1 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Dysgeusia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Headache 0/9 (0%) 0 1/7 (14.3%) 1 0/8 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 3/11 (27.3%) 4 0/8 (0%) 0 1/8 (12.5%) 1 3/18 (16.7%) 3 4/18 (22.2%) 5 0/18 (0%) 0 1/18 (5.6%) 1 1/15 (6.7%) 1 1/14 (7.1%) 1 1/13 (7.7%) 1 3/13 (23.1%) 4 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Hypoaesthesia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Paraesthesia 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Sinus headache 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Somnolence 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Tremor 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Psychiatric disorders
Anxiety 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Dysthymic disorder 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Insomnia 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Renal and urinary disorders
Dysuria 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Respiratory, thoracic and mediastinal disorders
Cough 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1
Dyspnoea 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Hiccups 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Nasal congestion 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Oropharyngeal pain 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 1/14 (7.1%) 1 0/13 (0%) 0 1/13 (7.7%) 2 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Paranasal sinus discomfort 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Rhinitis allergic 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Skin and subcutaneous tissue disorders
Dermatitis contact 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Dry skin 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Ecchymosis 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 1/8 (12.5%) 1 0/8 (0%) 0
Erythema 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 2 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Hyperhidrosis 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 1/14 (7.1%) 1 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Nail ridging 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Pruritus 1/9 (11.1%) 1 0/7 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 2 0/11 (0%) 0 2/11 (18.2%) 2 0/8 (0%) 0 2/8 (25%) 2 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 2/18 (11.1%) 2 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Rash 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/8 (12.5%) 1 1/8 (12.5%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Rash erythematous 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Rash maculo-papular 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/15 (6.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 1/8 (12.5%) 1 0/8 (0%) 0
Rash papular 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 1/8 (12.5%) 2 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 1/18 (5.6%) 1 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Rash pruritic 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 0/6 (0%) 0 1/8 (12.5%) 1 0/8 (0%) 0
Skin irritation 0/9 (0%) 0 1/7 (14.3%) 1 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0 1/6 (16.7%) 1 0/8 (0%) 0 0/8 (0%) 0
Skin wrinkling 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Vascular disorders
Flushing 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 1/18 (5.6%) 1 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0
Hypotension 0/9 (0%) 0 0/7 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/8 (0%) 0 0/8 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/18 (0%) 0 0/15 (0%) 0 0/14 (0%) 0 1/13 (7.7%) 1 0/13 (0%) 0 0/6 (0%) 0 0/8 (0%) 0 0/8 (0%) 0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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. Sponsor review can be expedited to meet publication timelines.

Results Point of Contact

Name/Title Senior Vice President, Global Clinical Development
Organization Merck Sharp & Dohme Corp.
Phone 1-800-672-6372
Email ClinicalTrialsDisclosure@merck.com
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT01982630
Other Study ID Numbers:
  • 8521-003
First Posted:
Nov 13, 2013
Last Update Posted:
Mar 8, 2022
Last Verified:
Dec 1, 2021