Type 2 Diabetes (T2D)
Conditions
Keywords
Type 2 diabetes (T2D)
Brief summary
This study will test the safety and tolerability of omarigliptin. It is hypothesized that administration of once-weekly omarigliptin in obese but otherwise healthy participants, and in obese participants with Type 2 diabetes (T2D) will be sufficiently safe and well tolerated to permit continued clinical investigation.
Interventions
DRUGOmarigliptin
Once-weekly 50 mg capsule
DRUGPlacebo
Once-weekly placebo capsule
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* obese (body mass index \[BMI\] ≥30 kg/m² and ≤40 kg/m²) male participants and female participants of non-childbearing potential * has been diagnosed with T2D (Panel B) * is not actively participating in a weight loss program
Exclusion criteria
* has a history of clinically-significant disease (other than T2D) * has a history of cancer * has estimated creatinine clearance ≤60 mL/min * is unable to refrain from or anticipates the use of any prescription or non-prescription medication * consumes excessive amounts of alcohol or caffeine * has participated in a previous omarigliptin study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Experiencing an Adverse Event (AE) | Up to Day 36 |
| Number of Participants Withdrawing From Study Therapy Due to an AE | Up to Day 22 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Inhibition of Dipeptidyl Peptidase-4 (DPP-4) After Day 15 | 168 hours post-dose on Day 15 | Percent DPP-4 inhibition at 168 hours after the Day 15 dose (from baseline \[pre-dose on Day 1\]) was compared in healthy and T2D participants receiving omarigliptin or placebo. |
| Percent Inhibition of DPP-4 After Day 22 | 168 hours post dose on Day 22 | Percent DPP-4 inhibition at 168 hours after the Day 22 dose (from baseline \[pre-dose on Day 1\]) was compared in healthy and T2D participants receiving omarigliptin or placebo. |
| WAA Active Glucagon-like Peptide-1 (GLP-1) Concentration | Through 4 hours post dose on Day 21 | Weighted average augmentation (WAA) active GLP-1 concentration was based on the 0.25, 0.5, 1, 2, and 4 hour timepoints. WAA was calculated as area under the curve (AUC) for the 4-hr post-dose time period (AUC0-4 hrs); this AUC was then divided by the time interval of 4 hours to obtain WAA. Log scale data were then back-transformed to obtain LS means. |
| WAA Total GLP-1 Concentration | Through 4 hours post dose on Day 21 | WAA total GLP-1 concentration was based on the 0.25, 0.5, 1, 2, and 4 hour timepoints. WAA was calculated as AUC0-4 hrs; this AUC was then divided by the time interval of 4 hours to obtain WAA. Log scale data were then back-transformed to obtain LS means. |
| Plasma Glucose Concentration | Through 4 hours post dose on Day 21 | Post-prandial glucose concentration is presented as a weighted average of the 0.25, 0.5, 1, 2, and 4 hour post-dose time points. Glucose concentration was calculated as area under the curve (AUC) for the 4-hr post-dose time period (AUC0-4 hrs); this AUC was then divided by the time interval of 4 hours to obtain weighted average glucose concentration. Log scale data were then back-transformed to obtain LS means. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Participants - Omarigliptin Obese healthy participants received once-weekly omarigliptin for 4 weeks. | 18 |
| T2D Participants (Panel B) Obese participants with T2D received once-weekly omarigliptin or placebo for 4 weeks. | 6 |
| T2D - Omarigliptin Obese T2D participants received once-weekly omarigliptin for 4 weeks. | 6 |
| T2D - Placebo Obese T2D participants received once-weekly placebo for 4 weeks. | 2 |
| Total | 32 |
Baseline characteristics
| Characteristic | Healthy Participants - Omarigliptin | T2D Participants (Panel B) | T2D - Omarigliptin | T2D - Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 52.3 Years STANDARD_DEVIATION 5.1 | 56.2 Years STANDARD_DEVIATION 7.6 | 55.4 Years STANDARD_DEVIATION 4.4 | 61.0 Years STANDARD_DEVIATION 8.5 | 54.2 Years STANDARD_DEVIATION 5.9 |
| Sex: Female, Male Female | 12 Participants | 4 Participants | 3 Participants | 1 Participants | 20 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 3 Participants | 1 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 18 | 2 / 6 | 4 / 6 | 2 / 2 |
| serious Total, serious adverse events | 0 / 18 | 0 / 6 | 0 / 6 | 0 / 2 |
Outcome results
Primary
Number of Participants Experiencing an Adverse Event (AE)
Time frame: Up to Day 36
Population: AEs were monitored in all obese healthy (Panel A) and Type 2 diabetes (T2D) (Panel B) participants who received omarigliptin 50 mg or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Omarigliptin | Number of Participants Experiencing an Adverse Event (AE) | 12 Participants |
| Healthy Placebo | Number of Participants Experiencing an Adverse Event (AE) | 2 Participants |
| T2D Omarigliptin | Number of Participants Experiencing an Adverse Event (AE) | 4 Participants |
| T2D Placebo | Number of Participants Experiencing an Adverse Event (AE) | 2 Participants |
Primary
Number of Participants Withdrawing From Study Therapy Due to an AE
Time frame: Up to Day 22
Population: AEs were monitored in all obese healthy (Panel A) and T2D (Panel B) participants who received omarigliptin 50 mg or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Omarigliptin | Number of Participants Withdrawing From Study Therapy Due to an AE | 0 Participants |
| Healthy Placebo | Number of Participants Withdrawing From Study Therapy Due to an AE | 0 Participants |
| T2D Omarigliptin | Number of Participants Withdrawing From Study Therapy Due to an AE | 0 Participants |
| T2D Placebo | Number of Participants Withdrawing From Study Therapy Due to an AE | 0 Participants |
Secondary
Percent Inhibition of Dipeptidyl Peptidase-4 (DPP-4) After Day 15
Percent DPP-4 inhibition at 168 hours after the Day 15 dose (from baseline \[pre-dose on Day 1\]) was compared in healthy and T2D participants receiving omarigliptin or placebo.
Time frame: 168 hours post-dose on Day 15
Population: Data from obese healthy participants (Panel A) and obese T2D participants (Panel B) 168 hours post-dose on Day 15 were pooled according to treatment. Predose data from Day 1 were missing from 2 participants.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Healthy Omarigliptin | Percent Inhibition of Dipeptidyl Peptidase-4 (DPP-4) After Day 15 | 91.92 Percent DPP-4 inhibition |
| Healthy Placebo | Percent Inhibition of Dipeptidyl Peptidase-4 (DPP-4) After Day 15 | 1.16 Percent DPP-4 inhibition |
90% CI: [82.7, 99.37]Difference in geometric means (GMs)
Secondary
Percent Inhibition of DPP-4 After Day 22
Percent DPP-4 inhibition at 168 hours after the Day 22 dose (from baseline \[pre-dose on Day 1\]) was compared in healthy and T2D participants receiving omarigliptin or placebo.
Time frame: 168 hours post dose on Day 22
Population: No data from obese healthy participants (Panel A) were collected after pre-dose on Day 22. Therefore, data are presented only for obese T2D participants (Panel B) 168 hours post-dose on Day 22.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Healthy Omarigliptin | Percent Inhibition of DPP-4 After Day 22 | 89.62 Percent DPP-4 inhibition |
| Healthy Placebo | Percent Inhibition of DPP-4 After Day 22 | -8.59 Percent DPP-4 inhibition |
Secondary
Plasma Glucose Concentration
Post-prandial glucose concentration is presented as a weighted average of the 0.25, 0.5, 1, 2, and 4 hour post-dose time points. Glucose concentration was calculated as area under the curve (AUC) for the 4-hr post-dose time period (AUC0-4 hrs); this AUC was then divided by the time interval of 4 hours to obtain weighted average glucose concentration. Log scale data were then back-transformed to obtain LS means.
Time frame: Through 4 hours post dose on Day 21
Population: Data from obese healthy participants (Panel A) and obese T2D participants (Panel B) 4 hours post dose on Day 21 were pooled according to treatment. All participants who received omarigliptin or placebo are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Healthy Omarigliptin | Plasma Glucose Concentration | 8.34 mg/dL |
| Healthy Placebo | Plasma Glucose Concentration | 20.84 mg/dL |
Secondary
WAA Active Glucagon-like Peptide-1 (GLP-1) Concentration
Weighted average augmentation (WAA) active GLP-1 concentration was based on the 0.25, 0.5, 1, 2, and 4 hour timepoints. WAA was calculated as area under the curve (AUC) for the 4-hr post-dose time period (AUC0-4 hrs); this AUC was then divided by the time interval of 4 hours to obtain WAA. Log scale data were then back-transformed to obtain LS means.
Time frame: Through 4 hours post dose on Day 21
Population: Data from obese healthy participants (Panel A) and obese T2D participants (Panel B) 4 hours post dose on Day 21 were pooled according to treatment. All participants who received omarigliptin or placebo are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Healthy Omarigliptin | WAA Active Glucagon-like Peptide-1 (GLP-1) Concentration | 3.84 pmol/L |
| Healthy Placebo | WAA Active Glucagon-like Peptide-1 (GLP-1) Concentration | 2.0 pmol/L |
90% CI: [1.55, 2.38]
Secondary
WAA Total GLP-1 Concentration
WAA total GLP-1 concentration was based on the 0.25, 0.5, 1, 2, and 4 hour timepoints. WAA was calculated as AUC0-4 hrs; this AUC was then divided by the time interval of 4 hours to obtain WAA. Log scale data were then back-transformed to obtain LS means.
Time frame: Through 4 hours post dose on Day 21
Population: Data from obese healthy participants (Panel A) and obese T2D participants (Panel B) 4 hours post dose on Day 21 were pooled according to treatment. All participants who received omarigliptin or placebo are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Healthy Omarigliptin | WAA Total GLP-1 Concentration | 2.11 pmol/L |
| Healthy Placebo | WAA Total GLP-1 Concentration | 2.31 pmol/L |
90% CI: [0.72, 1.17]