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NCT02055547

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

Completed Phase 1 Results posted Last updated 2 July 2020
What this trial tests

Phase 1 trial testing MK-8521 35μg in Type 2 Diabetes Mellitus in 61 participants. Completed in 17 September 2013.

Timeline
10 May 2013
Primary endpoint
17 September 2013
17 September 2013

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment61
Start date10 May 2013
Primary completion17 September 2013
Estimated completion17 September 2013

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 70, male only, with Type 2 Diabetes Mellitus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced at Least One Adverse Event (AE) (Part 1) Primary · From Day 1 through post-trial visit (Up to 8 weeks)

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 adver

GroupValue95% CI
Part 1 Panel A MK-8521 100μg3
Part 1 Panel A MK-8521 300μg4
Part 1 Panel B MK-8521 150μg2
Part 1 Panel B MK-8521 175μg0
Part 1 Panel B MK-8521 200μg5
Part 1, Pooled Placebo10
Number of Participants Who Discontinued Treatment Due to an AE (Part 1) Primary · Up to 8 weeks (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 adver

GroupValue95% CI
Part 1 Panel A MK-8521 100μg0
Part 1 Panel A MK-8521 300μg0
Part 1 Panel B MK-8521 150μg0
Part 1 Panel B MK-8521 175μg0
Part 1 Panel B MK-8521 200μg0
Part 1, Pooled Placebo1
Area Under the Concentration Time Curve of MK-8521 From 0 to Infinity (AUC0-∞) After a Single Dose (Part 1) Primary · Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-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.

GroupValue95% CI
Part 1 Panel A MK-8521 100μg48.7± 16.4
Part 1 Panel A MK-8521 300μg163± 6.37
Part 1 Panel B MK-8521 150μg84.4± 20.3
Part 1 Panel B MK-8521 175μg101± 6.07
Part 1 Panel B MK-8521 200μg109± 25.7
Peak Plasma Concentration (Cmax) of Participants Treated With a Single Dose of MK-8521 (Part 1) Primary · Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (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.

GroupValue95% CI
Part 1 Panel A MK-8521 100μg1.24± 30.2
Part 1 Panel A MK-8521 300μg4.29± 23.5
Part 1 Panel B MK-8521 150μg2.63± 20.0
Part 1 Panel B MK-8521 175μg3.10± 20.8
Part 1 Panel B MK-8521 200μg3.54± 18.4
Time Taken to Reach Cmax (Tmax) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1) Primary · Pre-dose, 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24, 30, 34, 48, 72, 96, 120 hrs. post-dose (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.

GroupValue95% CI
Part 1 Panel A MK-8521 100μg148 – 30
Part 1 Panel A MK-8521 300μg104 – 16
Part 1 Panel B MK-8521 150μg1110 – 16
Part 1 Panel B MK-8521 175μg128 – 12
Part 1 Panel B MK-8521 200μg1410 – 16
Apparent Terminal Half-life (t1/2) for Plasma Concentration of Participants Treated With a Single Dose of MK-8521 (Part 1) Primary · 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) 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.

GroupValue95% CI
Part 1 Panel A MK-8521 100μg13.8± 15.5
Part 1 Panel A MK-8521 300μg13.7± 8.93
Part 1 Panel B MK-8521 150μg14.8± 6.45
Part 1 Panel B MK-8521 175μg14.1± 2.64
Part 1 Panel B MK-8521 200μg13.8± 12.9
Number of Participants With an Adverse Event (AE) (Part 2) Primary · From Day 1 through post-trial visit (Up to 7 weeks)

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 adver

GroupValue95% CI
Part 2 Panel C MK-8521 50/72μg5
Part 2 Panel D MK-8521 100/150μg5
Part 2 Panel E MK-8521 125/150μg5
Part 2 Panel F MK-8521 72/125μg4
Part 2, Pooled Placebo3
Number of Participants Who Discontinued Treatment Due to an AE (Part 2) Primary · Up to 7 weeks (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 adver

GroupValue95% CI
Part 2 Panel C MK-8521 50/72μg0
Part 2 Panel D MK-8521 100/150μg1
Part 2 Panel E MK-8521 125/150μg0
Part 2 Panel F MK-8521 72/125μg0
Part 2, Pooled Placebo0
AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panels C, D, and E) Primary · Days 1, 5 and 10 (Part 2) (Panels C, D, 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 fo

Day 1
GroupValue95% CI
Part 2 Panel C MK-8521 50/72μg12.0± 21.3
Part 2 Panel D MK-8521 100/150μg23.1± 18.9
Part 2 Panel E MK-8521 125/150μg33.5± 16.4
Day 5
GroupValue95% CI
Part 2 Panel C MK-8521 50/72μg22.8± 20.7
Part 2 Panel D MK-8521 100/150μg43.3± 23.6
Part 2 Panel E MK-8521 125/150μg60.7± 19.8
Day 10
GroupValue95% CI
Part 2 Panel C MK-8521 50/72μg35.1± 19.0
Part 2 Panel D MK-8521 100/150μg86.8± 34.4
Part 2 Panel E MK-8521 125/150μg77.8± 15.0
AUC 0-24hr for Plasma Concentration of Participants Treated After Multiple Doses of MK-8521 (Part 2, Panel F) Primary · Days 1, 7 and 14 (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

Day 1
GroupValue95% CI
Part 2 Panel F MK-8521 72/125μg8.85± 22.1
Day 7
GroupValue95% CI
Part 2 Panel F MK-8521 72/125μg24.8± 21.6
Day 14
GroupValue95% CI
Part 2 Panel F MK-8521 72/125μg54.6± 17.9
Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panels C, D, and E) Primary · Days 1, 5 and 10 (Part 2) (Panels C, D, 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

Day 1
GroupValue95% CI
Part 2 Panel C MK-8521 50/72μg0.642± 21.8
Part 2 Panel D MK-8521 100/150μg1.25± 20.0
Part 2 Panel E MK-8521 125/150μg1.85± 23.1
Day 5
GroupValue95% CI
Part 2 Panel C MK-8521 50/72μg1.11± 22.6
Part 2 Panel D MK-8521 100/150μg2.21± 23.1
Part 2 Panel E MK-8521 125/150μg3.12± 16.0
Day 10
GroupValue95% CI
Part 2 Panel C MK-8521 50/72μg1.73± 20.4
Part 2 Panel D MK-8521 100/150μg4.31± 35.9
Part 2 Panel E MK-8521 125/150μg3.73± 13.0
Cmax for Plasma Concentration of Participants Treated With Multiple Doses of MK-8521 (Part 2, Panel F) Primary · Days 1, 7 and 14 (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

Day 1
GroupValue95% CI
Part 2 Panel F MK-8521 72/125μg0.511± 22.7
Day 7
GroupValue95% CI
Part 2 Panel F MK-8521 72/125μg1.15± 22.8
Day 14
GroupValue95% CI
Part 2 Panel F MK-8521 72/125μg2.56± 19.6

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 42. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1, Panel A, MK-8521 100μg
Serious: 0/7 (0%)
Deaths: 0/7
Part 1, Panel A, MK-8521 300μg
Serious: 0/5 (0%)
Deaths: 0/5
Part 1, Panel B, MK-8521 150μg
Serious: 0/6 (0%)
Deaths: 0/6
Part 1, Panel B, MK-8521 175μg
Serious: 0/3 (0%)
Deaths: 0/3
Part 1, Panel B, MK-8521 200μg
Serious: 0/5 (0%)
Deaths: 0/5
Part 2, Panel C, MK-8521 50μg/72μg
Serious: 0/6 (0%)
Deaths: 0/6
Part 2, Panel D, MK-8521 100μg/150μg
Serious: 0/6 (0%)
Deaths: 0/6
Part 2, Panel E, MK-8521 125μg/150μg
Serious: 0/6 (0%)
Deaths: 0/6
Part 2, Panel F, MK-8521 72μg/125μg
Serious: 0/6 (0%)
Deaths: 0/6
Part 3, Panel H, MK-8521 35μg
Serious: 0/11 (0%)
Deaths: 0/11
Part 3, Panel H, MK-8521 125μg
Serious: 0/12 (0%)
Deaths: 0/12
Pooled Placebo
Serious: 0/29 (0%)
Deaths: 0/29
Other adverse events (48 terms — click to expand)

ReactionSystemPart 1, Panel A, MK-8521 1…Part 1, Panel A, MK-8521 3…Part 1, Panel B, MK-8521 1…Part 1, Panel B, MK-8521 1…Part 1, Panel B, MK-8521 2…Part 2, Panel C, MK-8521 5…Part 2, Panel D, MK-8521 1…Part 2, Panel E, MK-8521 1…Part 2, Panel F, MK-8521 7…Part 3, Panel H, MK-8521 3…Part 3, Panel H, MK-8521 1…Pooled Placebo
NauseaGastrointestinal disorders
Catheter site painGeneral disorders
HeadacheNervous system disorders
VomitingGastrointestinal disorders
Dizziness posturalNervous system disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Catheter site haematomaGeneral disorders
Catheter site related reactionGeneral disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
SomnolenceNervous system disorders
Abdominal discomfortGastrointestinal disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
AstheniaGeneral disorders
Catheter site inflammationGeneral disorders
Chest discomfortGeneral disorders
Influenza like illnessGeneral disorders
Injection site haematomaGeneral disorders
Injection site painGeneral disorders
Vessel puncture site painGeneral disorders
Ear infectionInfections and infestations
NasopharyngitisInfections and infestations
SunburnInjury, poisoning and procedural complications
WoundInjury, poisoning and procedural complications
Increased appetiteMetabolism and nutrition disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
HypoaesthesiaNervous system disorders
MigraineNervous system disorders
ParaesthesiaNervous system disorders
Post-traumatic headacheNervous system disorders
PresyncopeNervous system disorders
SyncopeNervous system disorders
DysuriaRenal and urinary disorders
ProstatitisReproductive system and breast disorders
CoughRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT02055547 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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