A Single and Multiple-Dose Study of MK-8521 in Healthy and Obese Males (MK-8521-002)

NCT02055547 | Completed Phase 1 Results

• 3 other identifiers: 8521-0022013-000083-28MK-8521-002
• Study Type: interventional
• Target: 61
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MK-8521. Part 1 primary hypothesis: Administration of single subcutaneous (SC) doses of MK-8521 is sufficiently safe and well- tolerated in healthy participants, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation. Part 2: Administration of multiple once daily SC doses of MK-8521 is sufficiently safe and well-tolerated in healthy lean and obese participants, based on assessment of clinical and laboratory adverse experiences, to permit continued clinical investigation.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (21)

• Number of Participants Who Experienced at Least One Adverse Event (AE) (Part 1)

  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.

  From Day 1 through post-trial visit (Up to 8 weeks)

• Number of Participants Who Discontinued Treatment Due to an AE (Part 1)

  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.

  Up to 8 weeks (Part 1)

• Area Under the Concentration Time Curve of MK-8521 From 0 to Infinity (AUC0-∞) After a Single Dose (Part 1)

  AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 \[100-300μg\]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.

  Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (Part 1)

• Peak Plasma Concentration (Cmax) of Participants Treated With a Single Dose of MK-8521 (Part 1)

  Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 \[100-300μg\]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.

  Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (Part 1)

• Time Taken to Reach Cmax (Tmax) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1)

  Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 \[100-300μg\]) is presented. No pharmacokinetic analysis was performed on participants receiving Placebo.

  Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (Part 1)

• Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1)

  Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 \[100-300μg\]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.

  Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (Part 1)

• Number of Participants With an Adverse Event (AE) (Part 2)

  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.

  From Day 1 through post-trial visit (Up to 7 weeks)

• Number of Participants Who Discontinued Treatment Due to an AE (Part 2)

  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.

  Up to 7 weeks (Part 2)

• AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)

  AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part II, Panel C, D, and E) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

  Days 1, 5 and 10 (Part 2) (Panels C, D, E)

• AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panel F)

  AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

  Days 1, 7 and 14 (Part 2) (Panel F)

• Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)

  Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, E and F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C-E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

  Days 1, 5 and 10 (Part 2) (Panels C, D, E)

• Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)

  AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

  Days 1, 7 and 14 (Part 2) (Panel F)

• Trough Plasma Concentration (Ctrough) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)

  Trough plasma concentration (measured concentration at the end of a dosing interval at steady state \[taken directly before next administration\]). Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

  Days 1, 5 and 10 (Part 2) (Panels C, D, E)

• Trough Plasma Concentration (Ctrough) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)

  Trough plasma concentration (measured concentration at the end of a dosing interval at steady state \[taken directly before next administration\]). Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

  Days 1, 7 and 14 (Part 2) (Panel F)

• Tmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E)

  Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

  Days 1, 5 and 10 (Part 2) (Panels C, D, E)

• Tmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)

  Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections occurred at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

  Days 1, 7 and 14 (Part 2) (Panel F)

• Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part C, D, and E)

  Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). Apparent terminal t1/2 was not reported for certain days since the terminal phase was not adequately captured with sampling up to 24hr post dose. No pharmacokinetic analysis was performed on participants receiving Placebo. Blood was collected for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

  Days 1, 5 and 10 (Part 2) (Panels C, D, E)

• Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Part F)

  Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). Apparent terminal t1/2 was not reported for certain days since the terminal phase was not adequately captured with sampling up to 24hr post dose. No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections occurred at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

  Days 1, 7 and 14 (Part 2) (Panel F)

• Number of Participants With an Adverse Event (AE) (Part 3)

  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.

  Up to 6 weeks (Part 3)

• Number of Participants Who Discontinued Treatment Due to an AE (Part 3)

  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.

  Up to 6 weeks (Part 3)

• Average Concentration (Cave) of MK-8521 Corresponding to Slope of Insulin Secretion Rate/Glucose (ISR/G) During Graded Glucose Infusion (GGI) at Tmax After a Single Dose of MK-8521 (Part 3)

  Pancreatic beta cell sensitivity to ambient glucose concentration after a single dose of MK-8521 125μg/35μg or placebo at Tmax was quantified as the slope of insulin secretion rate relative to glucose concentration (ISR/G) during GGI (160 minutes duration) and assessed against MK-8521 average plasma concentration (Cave) during the GGI to preliminarily characterize the PK/ pharmacodynamic (PD) relationship. Study drug was administered on Day -1. Plasma concentrations of MK-8521 were determined at -10 min pre-GGI and 40, 80, 120 \& 160 min and blood concentrations of glucose, insulin \& C-peptide were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140 \& 160 minutes after start of GGI on Day 1 of each period. ISR calculated by deconvolution of C-peptide concentrations using a two-compartmental model was regressed on glucose concentration via simple linear regression; beta cell glucose sensitivity was defined as slope from the regression line.

  From -10 to 160 minutes after GGI on Day 1 (Part 3)

Secondary Outcomes (18)

• Change From Baseline in Time-weighted Average From 0 to 24 Hrs (TWA0-24hr) of Heart Rate (HR) After a Single Dose of MK-8521 (Part 1)

  Baseline (predose), up to 24 hours post-dose on Day 1, up to 24 hours post-dose on Day 2 (Part 1)

• Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Systolic Blood Pressure (SBP) of Participants Treated With A Single Dose of MK-8521 (Part 1)

  Baseline (predose), up to 24 hours post-dose on Day 1, up to 24 hours post-dose on Day 2 (Part 1)

• Change From Baseline in TWA 0-24 Hrs. Semi-recumbent Diastolic Blood Pressure (DBP) of Participants Treated With A Single Dose of MK-8521 (Part 1)

  Baseline (predose), up to 24 hours post-dose on Day 1, up to 24 hours post-dose on Day 2 (Part 1)

• Change From Baseline in TWA 0-24 Hrs. Heart Rate (HR) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel C, D, and E)

  Baseline (predose; up to 16 hrs on Day -1), predose & up to 24 hours postdose on Days 1, 6, and 10

• Change From Baseline in TWA 0-24 Hrs. Heart Rate (HR) of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F)

  Baseline (predose; up to 16 hrs on Day -1), predose & up to 24 hours postdose on Days 1, 8, and 14

Study Arms (19)

Part 1 - Panel A - MK-8521 100μg > PBO

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg in the first treatment period, and matching placebo (PBO) in the second treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 100μg; Drug: Placebo

Part 1 - Panel A - PBO > MK-8521 300μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, and MK-8521 300μg in the second treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 300μg; Drug: Placebo

Part 1 - Panel A - MK-8521 100μg > MK-8521 300μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg in the first treatment period, and MK-8521 300μg in the second treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 100μg; Drug: MK-8521 300μg

Part 1 - Panel B - MK-8521 150μg > PBO > MK-8521 175μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, PBO in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 150μg; Drug: MK-8521 175μg; Drug: Placebo

Part 1- Panel B- MK-8521 150μg > MK-8521 200μg > MK-8521 175μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, MK-8521 200μg in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 150μg; Drug: MK-8521 175μg; Drug: MK-8521 200μg

Part 1 - Panel B - MK-8521 150μg > MK-8521 200μg > PBO

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 150μg in the first treatment period, MK-8521 200μg in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 150μg; Drug: MK-8521 200μg; Drug: Placebo

Part 1 - Panel B - PBO > MK-8521 200μg > MK-8521 175μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received PBO in the first treatment period, MK-8521 200μg in the second treatment period, and MK-8521 175μg in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 175μg; Drug: MK-8521 200μg; Drug: Placebo

Part 2 - Panel C - MK-8521 50μg > MK-8521 72μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 50μg Days 1 to 5 and MK-8521 72μg Days 6 to 10 in a single treatment period.

Drug: MK-8521 50/72μg

Part 2 - Panel D - MK-8521 100μg > MK-8521 150μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 100μg Days 1 to 5 and MK-8521 150μg Days 6 to 10 in a single treatment period.

Drug: MK-8521 100μg; Drug: MK-8521 100/150μg

Part 2 - Panel E - MK-8521 125μg > MK-8521 150μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg Days 1 to 5 and MK-8521 150μg Days 6 to 10 in a single treatment period.

Drug: MK-8521 125μg; Drug: MK-8521 125/150μg

Part 2 - Panel F - MK-8521 72μg > MK-8521 125μg

EXPERIMENTAL

Obese male participants of 45 to 65 years of age received a single dose of MK-8521 72μg Days 1 to 7 and MK-8521 125μg Days 8 to 14 in a single treatment period.

Drug: MK-8521 125μg; Drug: MK-8521 72/125μg

Part 2 - Panels C+D+E - Pooled Placebo

PLACEBO COMPARATOR

Healthy male participants of 18 to 45 years of age received PBO once daily for 10 days.

Drug: Placebo

Part 2 - Panel F - Placebo

PLACEBO COMPARATOR

Obese male participants of 45 to 65 years of age received a single dose of PBO Days 1 to 14.

Drug: Placebo

Part 3 - Panel H - MK-8521 125μg > MK-8521 35μg > PBO

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg (high dose) in the first treatment period, MK-8521 35μg (low dose) in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 35μg; Drug: MK-8521 125μg; Drug: Placebo

Part 3 - Panel H - MK-8521 35μg > PBO > MK-8521 125μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 35μg (low dose) in the first treatment period, PBO MK-8521 in the second treatment period, and 125μg (high dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 35μg; Drug: MK-8521 125μg; Drug: Placebo

Part 3 - Panel H - PBO > MK- 8521 125μg > MK-8521 35μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, MK- 8521 125μg (high dose) in the second treatment period, and MK-8521 35μg (low dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 35μg; Drug: MK-8521 125μg; Drug: Placebo

Part 3 - Panel H - PBO > MK- 8521 35μg > MK-8521 125μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of PBO in the first treatment period, MK- 8521 35μg (low dose) in the second treatment period, and MK-8521 125μg (high dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 35μg; Drug: MK-8521 125μg; Drug: Placebo

Part 3 - Panel H - MK-8521 125μg > PBO > MK-8521 35μg

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 125μg (high dose) in the first treatment period, PBO in the second treatment period, and MK-8521 35μg (low dose) in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 35μg; Drug: MK-8521 125μg; Drug: Placebo

Part 3 - Panel H - MK-8521 35μg > MK-8521 125μg > PBO

EXPERIMENTAL

Healthy male participants of 18 to 45 years of age received a single dose of MK-8521 35μg (low dose) in the first treatment period, MK-8521 125μg (high dose) in the second treatment period, and PBO in the third treatment period. There was a minimum of a 7-day washout period between treatment periods.

Drug: MK-8521 35μg; Drug: MK-8521 125μg; Drug: Placebo

Interventions

MK-8521 35μg DRUG

Single dose 35μg subcutaneous (SC) injection in a treatment period (Part 3, Panel H)

Part 3 - Panel H - MK-8521 125μg > MK-8521 35μg > PBO; Part 3 - Panel H - MK-8521 125μg > PBO > MK-8521 35μg; Part 3 - Panel H - MK-8521 35μg > MK-8521 125μg > PBO; Part 3 - Panel H - MK-8521 35μg > PBO > MK-8521 125μg; Part 3 - Panel H - PBO > MK- 8521 125μg > MK-8521 35μg; Part 3 - Panel H - PBO > MK- 8521 35μg > MK-8521 125μg

MK-8521 100μg DRUG

Single dose 100μg SC injection in a treatment period (Part 1, Panel A) and (Part 2, Panel D)

Part 1 - Panel A - MK-8521 100μg > MK-8521 300μg; Part 1 - Panel A - MK-8521 100μg > PBO; Part 2 - Panel D - MK-8521 100μg > MK-8521 150μg

MK-8521 125μg DRUG

Single dose 125μg SC injection in a treatment period (Part 2, Panel E) and (Part 3, Panel H)

Part 2 - Panel E - MK-8521 125μg > MK-8521 150μg; Part 2 - Panel F - MK-8521 72μg > MK-8521 125μg; Part 3 - Panel H - MK-8521 125μg > MK-8521 35μg > PBO; Part 3 - Panel H - MK-8521 125μg > PBO > MK-8521 35μg; Part 3 - Panel H - MK-8521 35μg > MK-8521 125μg > PBO; Part 3 - Panel H - MK-8521 35μg > PBO > MK-8521 125μg; Part 3 - Panel H - PBO > MK- 8521 125μg > MK-8521 35μg; Part 3 - Panel H - PBO > MK- 8521 35μg > MK-8521 125μg

MK-8521 150μg DRUG

Single dose 150μg SC injection in a treatment period (Part 1, Panel B)

Part 1 - Panel B - MK-8521 150μg > MK-8521 200μg > PBO; Part 1 - Panel B - MK-8521 150μg > PBO > MK-8521 175μg; Part 1- Panel B- MK-8521 150μg > MK-8521 200μg > MK-8521 175μg

MK-8521 175μg DRUG

Single dose 175μg SC injection in a treatment period (Part 1, Panel B)

Part 1 - Panel B - MK-8521 150μg > PBO > MK-8521 175μg; Part 1 - Panel B - PBO > MK-8521 200μg > MK-8521 175μg; Part 1- Panel B- MK-8521 150μg > MK-8521 200μg > MK-8521 175μg

MK-8521 200μg DRUG

Single dose MK-8521 200μg SC injection in a treatment period (Part 1, Panel B)

Part 1 - Panel B - MK-8521 150μg > MK-8521 200μg > PBO; Part 1 - Panel B - PBO > MK-8521 200μg > MK-8521 175μg; Part 1- Panel B- MK-8521 150μg > MK-8521 200μg > MK-8521 175μg

MK-8521 300μg DRUG

Single dose 300μg SC injection in a treatment period (Part 1, Panel A)

Part 1 - Panel A - MK-8521 100μg > MK-8521 300μg; Part 1 - Panel A - PBO > MK-8521 300μg

MK-8521 50/72μg DRUG

MK-8521 50μg SC injection Days 1-5 and 72μg Days 6-10 (Part 2, Panel C)

Part 2 - Panel C - MK-8521 50μg > MK-8521 72μg

MK-8521 72/125μg DRUG

MK-8521 72μg SC injection Days 1-7 and 125μg Days 8-14 (Part 2, Panel F)

Part 2 - Panel F - MK-8521 72μg > MK-8521 125μg

MK-8521 100/150μg DRUG

MK-8521 100μg SC injection Days 1-5 and 150μg Days 6-10 SC in a treatment period (Part 2, Panel D)

Part 2 - Panel D - MK-8521 100μg > MK-8521 150μg

MK-8521 125/150μg DRUG

MK-8521 SC 125μg SC injection Days 1-5 and 150μg Days 6-10 (Part 2, Panel E)

Part 2 - Panel E - MK-8521 125μg > MK-8521 150μg

Placebo DRUG

Placebo to MK-8521 SC injection in a treatment period (Parts 1, 2, and 3)

Part 1 - Panel A - MK-8521 100μg > PBO; Part 1 - Panel A - PBO > MK-8521 300μg; Part 1 - Panel B - MK-8521 150μg > MK-8521 200μg > PBO; Part 1 - Panel B - MK-8521 150μg > PBO > MK-8521 175μg; Part 1 - Panel B - PBO > MK-8521 200μg > MK-8521 175μg; Part 2 - Panel F - Placebo; Part 2 - Panels C+D+E - Pooled Placebo; Part 3 - Panel H - MK-8521 125μg > MK-8521 35μg > PBO; Part 3 - Panel H - MK-8521 125μg > PBO > MK-8521 35μg; Part 3 - Panel H - MK-8521 35μg > MK-8521 125μg > PBO; Part 3 - Panel H - MK-8521 35μg > PBO > MK-8521 125μg; Part 3 - Panel H - PBO > MK- 8521 125μg > MK-8521 35μg; Part 3 - Panel H - PBO > MK- 8521 35μg > MK-8521 125μg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males of either 18 to 45 or 45 to 70 years of age depending on the component of the study
• Body Mass Index between either 18-25 or 30-40 kg/m\^2 depending on the component of the study
• Is in good health
• Is a non-smoker and/or has not used nicotine for at least 3 months

You may not qualify if:

• Is mentally or legally incapacitated, has significant emotional problems or has a history of psychiatric disorders in the past 5 years
• Has a history of the following abnormalities or diseases: endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological.
• History of cancer
• History of significant multiple or severe allergies or has had an anaphylactic reaction or significant intolerability to drugs or food
• Positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
• Had major surgery, donated or lost 1 unit (500 mL) of blood or participated in another study within prior 4 weeks
• Has irritable bowel disease or recurrent nausea, vomiting, diarrhea or abdominal pain
• History of acute or chronic pancreatitis
• Uses 2 weeks prior to trial, or anticipates using during trial, medications, drugs or herbal remedies such as St. John's Wort
• Consumes greater than 3 glasses of alcohol per day
• Consumes greater than 6 servings of caffeinated beverages per day
• Regularly uses illicit drugs or has a history of drug (including alcohol) abuse within prior 3 months
• Has known hypersensitivity to glucagon or any glucagon like peptide 1 (GLP-1) receptor agonist
• Is unwilling/unable to consume standardized meals and/or is on a carbohydrate restricted diet
• Has history of hypersensitivity to pharmacologic insulins

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Study Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parts 1 and 2 were parallel in design and Part 3 was crossover in design.

Study Record Dates

• First Submitted: February 4, 2014
• First Posted: February 5, 2014
• Study Start: May 10, 2013
• Primary Completion: September 17, 2013
• Study Completion: September 17, 2013
• Last Updated: July 2, 2020
• Results First Posted: July 2, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share