Type 2 Diabetes Mellitus
Conditions
Keywords
SPIL1033, type 2 diabetes mellitus
Brief summary
SPIL1033 resembles a gut hormone, which increases the insulin secretion, thus helps in reducing blood glucose levels. The purpose of study is to establish safety and efficacy of SPIL1033
Detailed description
SPIL1033 is subcutaneous injection is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus. In this study, efficacy and safety of SPIL1033 will be evaluated. Subjects will receive SPIL1033 or placebo, 5 mcg twice daily for the first 4 weeks and 10 mcg twice daily for the remaining 20 weeks.
Interventions
DRUGSPIL1033
5 mcg twice daily for the first 4 weeks and 10 mcg twice daily for the remaining 20 weeks. To be self-administered twice daily.
DRUGPlacebo
5 mcg twice daily for the first 4 weeks and 10 mcg twice daily for the remaining 20 weeks. To be self-administered twice daily.
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects 20 years of age and older. * Established clinical diagnosis of type 2 diabetes mellitus treated with diet and exercise or anti-diabetic agents as monotherapy or combination therapy. * Weight stable: their weight should not have varied more than 10% of screening visit weight, within 6 months prior to screening visit. * Women of child bearing potential practicing an acceptable method of birth control as judged by the investigator(s); with a negative urine pregnancy test. * Willing to participate and give written informed consent.
Exclusion criteria
* Previous exposure to exenatide (anti-exenatide antibodies at screening) or a glucagon-like peptide (GLP-1) analogue. * Used drugs for weight loss (for example, orlistat, sibutramine, phenylpropanolamine, rimonabant, or similar over-the-counter medications) within 3 months of screening. * Received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of trial entry. * Severe renal impairment (creatinine clearance \<30 ml/min) or end stage renal disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline to End of Study in Hemoglobin A1c (HbA1c) | 24 weeks |
| Change From Baseline to End of Study in Fasting Plasma Glucose (FPG) | 24 weeks |
| Count and Percentage of Subjects Positive for Anti-exenatide Antibodies | 24 weeks |
| Count and Percentage of Subjects With Potentially Immune-related Treatment-emergent Adverse Events (TEAEs) | 24 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in Body Weight | 24 weeks |
| Subjects Achieving Hemoglobin A1c (HbA1c) < 7% | 24 weeks |
| Change From Baseline in 2hour Postprandial Glucose (2-h PPG) | 24 weeks |
| Change From Baseline in Total Cholesterol | 24 weeks |
| Change From Baseline in Very Low Density Lipoproteins | 24 weeks |
| Change From Baseline in Triglycerides | 24 weeks |
| Change From Baseline in Low Density Lipoproteins | 24 weeks |
| Change From Baseline in High Density Lipoproteins | 24 weeks |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SPIL1033 SPIL1033: 5 mcg twice daily for the first 4 weeks and 10 mcg twice daily for the remaining 20 weeks. To be self-administered twice daily.
168 are the number of subjects in mITT population | 168 |
| Placebo Placebo: 5 mcg twice daily for the first 4 weeks and 10 mcg twice daily for the remaining 20 weeks. To be self-administered twice daily.
170 are the number of subjects in mTT population. | 170 |
| Total | 338 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 14 | 8 |
| Overall Study | Non-completion of visit activity | 0 | 1 |
| Overall Study | Protocol Violation | 5 | 1 |
| Overall Study | Subject non-compliance | 4 | 3 |
| Overall Study | Withdrawal by Subject | 19 | 15 |
Baseline characteristics
| Characteristic | Placebo | Total | SPIL1033 |
|---|---|---|---|
| Age, Continuous | 51.9 years STANDARD_DEVIATION 9.56 | 52.4 years STANDARD_DEVIATION 9.41 | 52.9 years STANDARD_DEVIATION 9.26 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 170 Participants | 338 Participants | 168 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 86 Participants | 169 Participants | 83 Participants |
| Sex: Female, Male Male | 84 Participants | 169 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 180 | 0 / 180 |
| other Total, other adverse events | 126 / 180 | 115 / 180 |
| serious Total, serious adverse events | 6 / 180 | 1 / 180 |
Outcome results
Primary
Change From Baseline to End of Study in Fasting Plasma Glucose (FPG)
Time frame: 24 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPIL1033 | Change From Baseline to End of Study in Fasting Plasma Glucose (FPG) | 0.48 mg/dL | Standard Error 9.78 |
| Placebo | Change From Baseline to End of Study in Fasting Plasma Glucose (FPG) | -5.42 mg/dL | Standard Error 10.21 |
95% CI: [-6.7565, 18.5535]
Primary
Change From Baseline to End of Study in Hemoglobin A1c (HbA1c)
Time frame: 24 weeks
Population: Intent-to-treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPIL1033 | Change From Baseline to End of Study in Hemoglobin A1c (HbA1c) | -0.227 percentage of hemoglobin A1c (HbA1c) | Standard Error 0.243 |
| Placebo | Change From Baseline to End of Study in Hemoglobin A1c (HbA1c) | -0.227 percentage of hemoglobin A1c (HbA1c) | Standard Error 0.254 |
95% CI: [-0.31377, 0.31418]
Primary
Count and Percentage of Subjects Positive for Anti-exenatide Antibodies
Time frame: 24 weeks
Population: modified intent to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SPIL1033 | Count and Percentage of Subjects Positive for Anti-exenatide Antibodies | 59 Participants |
| Placebo | Count and Percentage of Subjects Positive for Anti-exenatide Antibodies | 2 Participants |
p-value: <0.0001Mantel Haenszel
Primary
Count and Percentage of Subjects With Potentially Immune-related Treatment-emergent Adverse Events (TEAEs)
Time frame: 24 weeks
Population: Evaluable population for safety: subjects who were randomized and received at least one dose of a trial medication
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SPIL1033 | Count and Percentage of Subjects With Potentially Immune-related Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Placebo | Count and Percentage of Subjects With Potentially Immune-related Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
Secondary
Change From Baseline in 2hour Postprandial Glucose (2-h PPG)
Time frame: 24 weeks
Population: The evaluable population: all mITT subjects who received at least 80% of study medication over 24 weeks and completed treatment through week 24. (modified Intent-to-treat population: .subjects who were randomized and received at least one dose of the trial medication after visit 2 (baseline) and had at least one post-baseline visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SPIL1033 | Change From Baseline in 2hour Postprandial Glucose (2-h PPG) | -21.20 mg/dl | Standard Deviation 14.5 |
| Placebo | Change From Baseline in 2hour Postprandial Glucose (2-h PPG) | -16.83 mg/dl | Standard Deviation 14.49 |
p-value: 0.6318ANCOVA
Secondary
Change From Baseline in High Density Lipoproteins
Time frame: 24 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPIL1033 | Change From Baseline in High Density Lipoproteins | 0.64 mg/dL | Standard Error 2.16 |
| Placebo | Change From Baseline in High Density Lipoproteins | 0.62 mg/dL | Standard Error 2.16 |
p-value: 0.99ANOVA
Secondary
Change From Baseline in Low Density Lipoproteins
Time frame: 24 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPIL1033 | Change From Baseline in Low Density Lipoproteins | -3.18 mg/dL | Standard Error 6.12 |
| Placebo | Change From Baseline in Low Density Lipoproteins | 0.15 mg/dL | Standard Error 6.12 |
p-value: 0.3813ANOVA
Secondary
Change From Baseline in Total Cholesterol
Time frame: 24 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPIL1033 | Change From Baseline in Total Cholesterol | -4.89 mg/dL | Standard Error 7.4 |
| Placebo | Change From Baseline in Total Cholesterol | -0.11 mg/dL | Standard Error 7.4 |
p-value: 0.2984ANOVA
Secondary
Change From Baseline in Triglycerides
Time frame: 24 weeks
Population: The evaluable population: all mITT subjects who received at least 80% of study medication over 24 weeks and completed treatment through week 24. (modified Intent-to-treat population: .subjects who were randomized and received at least one dose of the trial medication after visit 2 (baseline) and had at least one post-baseline visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPIL1033 | Change From Baseline in Triglycerides | 1.27 mg/dl | Standard Error 16.53 |
| Placebo | Change From Baseline in Triglycerides | 8.39 mg/dl | Standard Error 16.53 |
p-value: 0.4887ANOVA
Secondary
Change From Baseline in Very Low Density Lipoproteins
Time frame: 24 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPIL1033 | Change From Baseline in Very Low Density Lipoproteins | 0.88 mg/dL | Standard Error 3.13 |
| Placebo | Change From Baseline in Very Low Density Lipoproteins | 1.55 mg/dL | Standard Error 3.13 |
p-value: 0.7324ANOVA
Secondary
Change in Body Weight
Time frame: 24 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SPIL1033 | Change in Body Weight | -1.708 kilograms | Standard Error 0.468 |
| Placebo | Change in Body Weight | -0.792 kilograms | Standard Error 0.467 |
p-value: 0.0017ANOVA
Secondary
Subjects Achieving Hemoglobin A1c (HbA1c) < 7%
Time frame: 24 weeks
Population: Evaluable Population for Efficacy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SPIL1033 | Subjects Achieving Hemoglobin A1c (HbA1c) < 7% | 26 Participants |
| Placebo | Subjects Achieving Hemoglobin A1c (HbA1c) < 7% | 20 Participants |
p-value: 0.6098Mantel Haenszel