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

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 to 70 years
• Men only
• Healthy volunteers accepted
• Adult, Older adult

About this study

Official title: A Single and Multiple-Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8521 in Subjects

Conditions

Type 2 Diabetes Mellitus

Being tested

MK-8521 35μg, MK-8521 100μg, MK-8521 125μg, MK-8521 150μg, MK-8521 175μg

Medical subject headings

Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• MK-8521 35μgDrug

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

• MK-8521 100μgDrug

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

• MK-8521 125μgDrug

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

• MK-8521 150μgDrug

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

• MK-8521 175μgDrug

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

• MK-8521 200μgDrug

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

• MK-8521 300μgDrug

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

• MK-8521 50/72μgDrug

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

• MK-8521 72/125μgDrug

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

• MK-8521 100/150μgDrug

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

• MK-8521 125/150μgDrug

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

• PlaceboDrug

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

What is being measured

The primary outcome is the main question the study is designed to answer.

1. 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.

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

2. 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.

   Measured: Up to 8 weeks (Part 1)

3. 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.

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

4. 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.

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

5. 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.

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

6. 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.

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

7. 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.

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

8. 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.

   Measured: Up to 7 weeks (Part 2)

9. 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.

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

10. 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.

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

11. 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.

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

12. 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.

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

13. 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.

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

14. 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.

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

15. 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.

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

16. 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.

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

17. 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.

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

18. 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.

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

19. 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.

    Measured: Up to 6 weeks (Part 3)

20. 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.

    Measured: Up to 6 weeks (Part 3)

21. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted5 Feb 2014 (estimated)
2. Study start10 May 2013
3. Primary completion17 Sep 2013
4. Study completion17 Sep 2013

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
• More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.