Type 2 Diabetes
Conditions
Brief summary
A 2-period crossover study to assess the safety, tolerability and glucose-lowering effects of MK8245.
Detailed description
Hypothesis: Multiple doses of MK-8245 are sufficiently safe and well tolerated in patients with Type 2 diabetes based on an assessment of clinical and laboratory adverse experiences (AEs), to permit continued clinical investigation.
Interventions
DRUGMK8245
MK8245 50 mg capsules twice daily for 13 days. On Day 14, only the morning dose of study medication will be taken. There will be a 14 day washout period. Patients will then crossover to MK8245 placebo capsules twice daily for 13 days. On Day 14, only the morning dose of study drug will be taken.
DRUGComparator: Placebo
MK8245 placebo capsules twice daily for 13 days. On Day 14, only the morning dose of study medication will be taken. There will be a 14 day washout period. Patients will then crossover to MK8245 50 mg capsules twice daily for 13 days. On Day 14, only the morning dose of study drug will be taken.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subject has a diagnosis of Type 2 Diabetes and is being treated with diet and exercise alone or a single oral anti-hyperglycemic agent * Subject is willing to follow the weight-maintaining diet and exercise program or equivalent beginning 4 weeks before receiving study drug, throughout the study and until the post study visit * Subject has been a nonsmoker and/or has not used nicotine-containing products for at least approximately 6 months
Exclusion criteria
* Subject has a history of stroke, chronic seizures, or major neurological disorder * Subject has a history of neoplastic disease (except non-melanomatous skin carcinoma, carcinoma in situ of the cervix, other malignancies successfully treated at least 10 years prior to screening, or malignancies deemed highly unlikely to recur.) * Subject has a history of Type 1 Diabetes Mellitus and/or history of ketoacidosis * Subject has a history of contact lens use within approximately the previous 6 months * Subject has been diagnosed with dry eye syndrome * Subject has used lipid-lowering therapies in the past 3 months (Subjects on a stable monotherapy dose of statins may be included) * Subject has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks of starting in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | 56 days | An LAE is defined as any unfavorable & unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A CAE is defined similarly but also includes changes in structure or function of the body. Serious AEs are those occuring that result in one or more of the pre-specified outcome(s) that meet the criteria of seriousness, including death, life-threatening, significant disability, or hospitalization, etc. Drug-relatedness was determined by the investigator based on clinical judgement. |
| Mean Change From Baseline in Hepatic Glucose Production (HGP) at Day 14 | Day 14 of each 14-day Treatment Period | Changes in HGP were determined during a euglycemic clamp procedure. HGP was evaluated as milligrams per kilogram of glucose produced per minute. |
Other
| Measure | Time frame |
|---|---|
| Hepatic Glucose Production (HGP) at Baseline | Baseline |
Participant flow
Pre-assignment details
For subjects taking anti-hyperglycemic agents and who otherwise qualified for the study, a 4-week washout/run-in period was required prior to dosing.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Physician Decision | 1 | 0 |
| Treatment Period 1 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 49.43 years |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 14 | 5 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
Mean Change From Baseline in Hepatic Glucose Production (HGP) at Day 14
Changes in HGP were determined during a euglycemic clamp procedure. HGP was evaluated as milligrams per kilogram of glucose produced per minute.
Time frame: Day 14 of each 14-day Treatment Period
Population: Subjects who discontinued were not used in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK8245 | Mean Change From Baseline in Hepatic Glucose Production (HGP) at Day 14 | -1.09 mg/kg/min | Standard Deviation 1.54 |
| Placebo | Mean Change From Baseline in Hepatic Glucose Production (HGP) at Day 14 | -0.87 mg/kg/min | Standard Deviation 0.94 |
Primary
Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs)
An LAE is defined as any unfavorable & unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A CAE is defined similarly but also includes changes in structure or function of the body. Serious AEs are those occuring that result in one or more of the pre-specified outcome(s) that meet the criteria of seriousness, including death, life-threatening, significant disability, or hospitalization, etc. Drug-relatedness was determined by the investigator based on clinical judgement.
Time frame: 56 days
Population: All 14 subjects enrolled in the study were included in the assessment of safety and tolerability (although only 12 subjects received placebo, our database includes all subjects in the analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK8245 | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With clinical adverse events (CAEs) | 4 participants |
| MK8245 | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With drug-related CAEs | 0 participants |
| MK8245 | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With Serious CAEs | 0 participants |
| MK8245 | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With laboratory adverse events (LAEs) | 0 participants |
| MK8245 | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With drug-related LAEs | 0 participants |
| MK8245 | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With serious LAEs | 0 participants |
| Placebo | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With drug-related LAEs | 0 participants |
| Placebo | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With clinical adverse events (CAEs) | 5 participants |
| Placebo | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With laboratory adverse events (LAEs) | 0 participants |
| Placebo | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With drug-related CAEs | 0 participants |
| Placebo | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With serious LAEs | 0 participants |
| Placebo | Number of Participants Experiencing Clinical and Laboratory Adverse Events (CAEs and LAEs) | With Serious CAEs | 0 participants |
Other Pre-specified
Hepatic Glucose Production (HGP) at Baseline
Time frame: Baseline
Population: Subjects who discontinued were not used in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK8245 | Hepatic Glucose Production (HGP) at Baseline | 1.87 mg/kg/min | Standard Deviation 0.36 |
| Placebo | Hepatic Glucose Production (HGP) at Baseline | 1.95 mg/kg/min | Standard Deviation 0.36 |