Type 2 Diabetes Mellitus
Conditions
Brief summary
This study will evaluate the effect of dose escalation of once-weekly (QW) subcutaneous (SC) OPK-8003 injections vs placebo on HbA1c absolute change from baseline at 30 weeks in subjects with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise alone, or treated with a stable dose of metformin.
Detailed description
This clinical trial is a phase 2, double-blind dose escalation regimen of once-weekly OPK-88003 in subjects with T2DM. The trial consists of a screening/baseline (up to 2 weeks prior to first dose), treatment period consisting of a dose escalation (8 weeks) and a target dose (22 weeks), and a follow-up period (4 weeks). Subjects will be randomly assigned to volume-matched OPK-88003 or placebo administered QW.
Interventions
DRUGOPK-88003
OPK-88003 subcutaneous injection
DRUGPlacebo
Placebo subcutaneous injection
Sponsors
OPKO Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Men or women aged 18 to 80 years with T2DM treated with diet and exercise alone or on a stable dose of metformin (≥ 1000 mg/day), * BMI ≥27 and ≤45 kg/m2 * HbA1c ≥7.0% and ≤10.5% at screening
Exclusion criteria
* Type 1 diabetes mellitus * Previous treatment with incretin mimetic drugs * Have used insulin for diabetic control for more than 6 consecutive days within the prior year * Have had two or more emergency room visits or hospitalizations due to poor glucose control within the prior 6 months * Have a history of acute or chronic pancreatitis or elevation in serum lipase/amylase (\>2 x ULN).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c in Subjects With Type 2 DM | From baseline to 30 weeks | To evaluate the effect of dose escalation of QW SC OPK-88003 vs placebo injections on HbA1c absolute change from baseline to after 30 weeks treatment in subjects with T2DM inadequately controlled with diet and exercise alone, or treated with a stable dose of metformin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent (%) Body Weight Change | From baseline to 30 weeks | Mean percent (%) body weight change from baseline to after 30 weeks treatment |
| Percent (%) of Subjects With 5% or Greater Body Weight Loss. | 30 weeks. | Percent (%) of subjects with 5% or greater body weight loss after 30 weeks treatment |
| Change From Baseline of Fasting Plasma Glucose (FPG). | 30 weeks. | Change of FPG from baseline to after 30 weeks treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Water for injection, Sorbitol, L-Methionine, Sodium Acetate Trihydrate
Placebo: Placebo subcutaneous injection | 41 |
| OPK-88003 70 mg/vial (extractable volume 1 mL)
OPK-88003: OPK-88003 subcutaneous injection | 72 |
| Total | 113 |
Baseline characteristics
| Characteristic | OPK-88003 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 53.8 Year STANDARD_DEVIATION 9.94 | 55.1 Year STANDARD_DEVIATION 9.75 | 57.4 Year STANDARD_DEVIATION 9.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 59 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 54 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 18 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 60 Participants | 93 Participants | 33 Participants |
| Sex: Female, Male Female | 29 Participants | 53 Participants | 24 Participants |
| Sex: Female, Male Male | 43 Participants | 60 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 72 |
| other Total, other adverse events | 5 / 41 | 35 / 72 |
| serious Total, serious adverse events | 2 / 41 | 9 / 72 |
Outcome results
Primary
Change in HbA1c in Subjects With Type 2 DM
To evaluate the effect of dose escalation of QW SC OPK-88003 vs placebo injections on HbA1c absolute change from baseline to after 30 weeks treatment in subjects with T2DM inadequately controlled with diet and exercise alone, or treated with a stable dose of metformin.
Time frame: From baseline to 30 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in HbA1c in Subjects With Type 2 DM | -0.25 mmols/mol | Standard Error 0.209 |
| OPK-88003 | Change in HbA1c in Subjects With Type 2 DM | -1.47 mmols/mol | Standard Error 0.168 |
Secondary
Change From Baseline of Fasting Plasma Glucose (FPG).
Change of FPG from baseline to after 30 weeks treatment
Time frame: 30 weeks.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline of Fasting Plasma Glucose (FPG). | -13.3 mg/dL | Standard Error 7.04 |
| OPK-88003 | Change From Baseline of Fasting Plasma Glucose (FPG). | -46.2 mg/dL | Standard Error 5.86 |
Secondary
Mean Percent (%) Body Weight Change
Mean percent (%) body weight change from baseline to after 30 weeks treatment
Time frame: From baseline to 30 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Percent (%) Body Weight Change | -2.10 Percentage of body weight change | Standard Error 0.976 |
| OPK-88003 | Mean Percent (%) Body Weight Change | -5.83 Percentage of body weight change | Standard Error 0.737 |
Secondary
Percent (%) of Subjects With 5% or Greater Body Weight Loss.
Percent (%) of subjects with 5% or greater body weight loss after 30 weeks treatment
Time frame: 30 weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percent (%) of Subjects With 5% or Greater Body Weight Loss. | 16.7 Percentage of participants |
| OPK-88003 | Percent (%) of Subjects With 5% or Greater Body Weight Loss. | 48.8 Percentage of participants |