Obesity and Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is to assess the effects of JNJ-64565111 compared with placebo in severely obese Type 2 Diabetes Mellitus (T2DM) participants after 12 weeks of treatment on: the percentage change in body weight from baseline and safety and tolerability.
Interventions
Participants will receive JNJ-64565111 Dose Level 1 SC once-weekly until Week 12.
Participants will receive JNJ-64565111 Dose Level 2 SC once-weekly until Week 12.
Participants will receive JNJ-64565111 Dose Level 3 SC once-weekly until Week 12.
DRUGPlacebo
Participants will receive matching placebo to JNJ-64565111 SC once-weekly until Week 12.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Body Mass Index (BMI) greater than or equal to (\>=) 35 to less than or equal to (\<=) 50 kilogram per meter square (kg/m\^2) at screening * Stable weight (that is, change of \<= 5 percent \[%\] within 12 weeks before screening based on medical or participant reported history) * Hemoglobin A1c of \>= 6.5% and \<= 9.5% at screening and meets one of the inclusion criteria as: (a) on diet and exercise alone \>= 12 weeks prior to screening; (b) on stable dose of single oral antihyperglycemic agent (AHA) or dual-combination oral AHAs for \>= 12 weeks prior to screening * Women must be either: (a) Postmenopausal, or (b) Permanently sterilized or otherwise be incapable of pregnancy, or (c) Heterosexually active and practicing a highly effective method of birth control, or (d) Not heterosexually active * Willing and able to adhere to specific the prohibitions and restrictions
Exclusion criteria
* History of obesity with a known secondary cause (example, Cushing's disease/syndrome) * History of Type 1 diabetes mellitus, diabetic ketoacidosis, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy * Fasting C-peptide less than (\<) 0.7 nanogram per milliliter (ng/mL) at screening * Fasting fingerstick glucose of \>= 270 milligram per deciliter (mg/dL) (\>=15 millimoles per liter \[mmol/L\]) on Day 1 * Ongoing, inadequately controlled thyroid disorder as assessed by the investigator's review of the participant's medical history. Participants taking thyroid hormone replacement therapy must be on stable doses for at least 6 weeks before the screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight at Week 12 | Baseline, Week 12 | Percent change from baseline in body weight in kilograms (kg) at Week 12 was reported. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to 16 Weeks | An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. An TEAE is defined as an AE with an onset after the initiation study medication and before the last study medication date of the double-blind (12-Week) treatment phase plus 35 Days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Body Weight at Week 12 | Baseline, Week 12 | Change from baseline in body weight at Week 12 was reported. |
| Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Weight Loss at Week 12 | Week 12 | Number of participants with \>= 5 % weight loss at Week 12 was reported. |
Countries
United States
Participant flow
Pre-assignment details
Total 196 participants were randomized out of which 175 participants completed study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants self-administered the matching placebo of JNJ-64565111 subcutaneously (SC) once-weekly throughout the 12-week treatment phase or until early discontinuation of study drug. | 49 |
| JNJ-64565111 5.0 mg Participants self-administered 5.0 milligram (mg) JNJ-64565111 SC once-weekly throughout the 12-week treatment phase or until early discontinuation of study drug. | 48 |
| JNJ-64565111 7.4 mg Participants self-administered 7.4 mg JNJ-64565111 SC once-weekly throughout the 12-week treatment phase or until early discontinuation of study drug. | 49 |
| JNJ-64565111 10.0 mg Participants self-administered 10.0 mg JNJ-64565111 SC once-weekly throughout the 12-week treatment phase or until early discontinuation of study drug. | 49 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 | 2 | 1 |
| Overall Study | Site terminated by Sponsor | 1 | 4 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | JNJ-64565111 10.0 mg | JNJ-64565111 7.4 mg | JNJ-64565111 5.0 mg |
|---|---|---|---|---|---|
| Age, Continuous | 57.4 years STANDARD_DEVIATION 9.09 | 56.6 years STANDARD_DEVIATION 9.04 | 56.2 years STANDARD_DEVIATION 8.57 | 57.8 years STANDARD_DEVIATION 8.97 | 55.1 years STANDARD_DEVIATION 9.56 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 51 Participants | 15 Participants | 14 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 144 Participants | 34 Participants | 35 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 52 Participants | 17 Participants | 13 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 36 Participants | 139 Participants | 31 Participants | 34 Participants | 38 Participants |
| Region of Enrollment UNITED STATES | 49 Participants | 195 Participants | 49 Participants | 49 Participants | 48 Participants |
| Sex: Female, Male Female | 30 Participants | 118 Participants | 28 Participants | 28 Participants | 32 Participants |
| Sex: Female, Male Male | 19 Participants | 77 Participants | 21 Participants | 21 Participants | 16 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 | 0 / 49 | 0 / 48 | 0 / 49 | 0 / 49 |
| other Total, other adverse events | 18 / 49 | 25 / 48 | 33 / 49 | 30 / 49 |
| serious Total, serious adverse events | 1 / 49 | 2 / 48 | 1 / 49 | 3 / 49 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. An TEAE is defined as an AE with an onset after the initiation study medication and before the last study medication date of the double-blind (12-Week) treatment phase plus 35 Days.
Time frame: Up to 16 Weeks
Population: Safety analysis set included include all randomized participants who had received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 28 Participants |
| JNJ-64565111 5.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 30 Participants |
| JNJ-64565111 7.4 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 39 Participants |
| JNJ-64565111 10.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 36 Participants |
Primary
Percent Change From Baseline in Body Weight at Week 12
Percent change from baseline in body weight in kilograms (kg) at Week 12 was reported.
Time frame: Baseline, Week 12
Population: Modified intent-to-treat (mITT) analysis set included all intent-to-treat (ITT) participants who had taken at least 1 dose of study drug and had at least 1 post-baseline body weight measurement. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Body Weight at Week 12 | -0.70 Percent Change | Standard Error 0.5 |
| JNJ-64565111 5.0 mg | Percent Change From Baseline in Body Weight at Week 12 | -5.25 Percent Change | Standard Error 0.57 |
| JNJ-64565111 7.4 mg | Percent Change From Baseline in Body Weight at Week 12 | -6.55 Percent Change | Standard Error 0.56 |
| JNJ-64565111 10.0 mg | Percent Change From Baseline in Body Weight at Week 12 | -7.92 Percent Change | Standard Error 0.55 |
p-value: <0.00195% CI: [-6.05, -3.06]Hochberg Approach
p-value: <0.00195% CI: [-7.34, -4.36]Hochberg Approach
p-value: <0.00195% CI: [-8.7, -5.75]Hochberg Approach
Secondary
Change From Baseline in Body Weight at Week 12
Change from baseline in body weight at Week 12 was reported.
Time frame: Baseline, Week 12
Population: mITT analysis set included all ITT participants who had taken at least 1 dose of study drug and had at least 1 post-baseline body weight measurement. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at Week 12 | -0.90 kg | Standard Error 0.577 |
| JNJ-64565111 5.0 mg | Change From Baseline in Body Weight at Week 12 | -5.92 kg | Standard Error 0.653 |
| JNJ-64565111 7.4 mg | Change From Baseline in Body Weight at Week 12 | -7.34 kg | Standard Error 0.648 |
| JNJ-64565111 10.0 mg | Change From Baseline in Body Weight at Week 12 | -9.04 kg | Standard Error 0.635 |
Secondary
Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Weight Loss at Week 12
Number of participants with \>= 5 % weight loss at Week 12 was reported.
Time frame: Week 12
Population: mITT analysis set included all ITT participants who had taken at least 1 dose of study drug and had at least 1 post-baseline body weight measurement.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Weight Loss at Week 12 | 1 Participants |
| JNJ-64565111 5.0 mg | Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Weight Loss at Week 12 | 20 Participants |
| JNJ-64565111 7.4 mg | Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Weight Loss at Week 12 | 20 Participants |
| JNJ-64565111 10.0 mg | Number of Participants With Greater Than or Equal to (>=) 5 Percent (%) Weight Loss at Week 12 | 30 Participants |