Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 diabetes, diabetes, diabetes mellitus, diabetes mellitus, type 2, non-TZD, thiazolidinedione, selective peroxisome proliferator-activated receptor gamma modulator, SPPARM, peroxisome proliferator-activated receptor gamma, PPAR gamma, insulin sensitizer, glucose control, endocrinopathy, hypoglycemic agent, sulfonylurea, metformin, pioglitazone, nutritional and metabolic diseases
Brief summary
This is a 24 week study comparing the efficacy of four dose levels of INT131 besylate with pioglitazone HCl in patients with type 2 diabetes. Eligible patients will be men and women (of non-childbearing potential or using dual barrier methods of contraception) between 30 and 75 years of age who are minimally responsive to treatment with sulfonylurea monotherapy or sulfonylurea plus metformin combination therapy.
Interventions
Sponsors
InteKrin Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Type 2 diabetes and on either sulfonylurea monotherapy or sulfonylurea plus metformin combination therapy for at least 3 months at stable dose * Males and Females (of non-childbearing potential or who are using dual barrier methods of contraception) between 30 and 75 years of age * HbA1c must be ≥7.5% and ≤10% at screening * Fasting Plasma Glucose must be \<240 mg/dL at screening
Exclusion criteria
* History of type 1 diabetes * History of diabetic ketoacidosis * NYHA Class III or IV cardiac status or hospitalization for congestive heart failure within 6 weeks prior to Visit 1 * Treatment with any non-peroxisome proliferator-activated receptor (non-PPAR) antidiabetic agent, investigational or approved, other than metformin or permitted sulfonylureas within 3 months prior to screening * Treatment with rosiglitazone, pioglitazone, or any PPAR investigational antidiabetic agent within 6 month prior to screening * Body mass index \>45 kg/m2 * Fasting triglycerides \>500 mg/dL * Uncontrolled hypertension (sitting systolic blood pressure \>160 mmHg and/or sitting diastolic blood pressure \>100 mmHg * Presence of diabetic complications, which in the opinion of the investigator, would complicate the subject's participation in the study (i.e., require initiation of new medication)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward | Weeks 0-24 | HbA1c is measured as percent. Thus this change from baseline reflects the week 24 HbA1c percent minus the Week 0 HbA1c percent |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward. | Weeks 0-24 | The change from baseline reflects the Week 24 FPG minus the Week 0 FPG with last observation carried forward. |
Countries
Mexico, United States
Participant flow
Pre-assignment details
Patients 30 - 75 years of age with type 2 diabetes mellitus with inadequate glycemic control (HbA1c ≥7.5% and ≤ 10% and a Fasting Plasma Glucose \<240 mg/dL) at screening on sulfonylurea monotherapy or sulfonylurea plus metformin were eligible to enter the study.
Participants by arm
| Arm | Count |
|---|---|
| INT131 Besylate 0.5 mg INT131 besylate 0.5 mg once-daily administration and matching placebo to pioglitazone. | 60 |
| INT131 Besylate 1 mg INT131 besylate 1 mg once-daily administration and matching placebo to pioglitazone | 61 |
| INT131 Besylate 2 mg INT131 besylate 2 mg administered once-daily and matching placebo to pioglitazone | 63 |
| INT131 Besylate 3 mg INT131 besylate 3 mg administered once-daily and matching placebo to pioglitazone | 61 |
| Pioglitazone HCl 45 mg pioglitazone HCl 45 mg administered once-daily and matching placebo to INT131 besylate | 60 |
| Placebo placebo administered once-daily | 61 |
| Total | 366 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 | 2 | 3 | 2 |
| Overall Study | Lost to Follow-up | 2 | 1 | 2 | 4 | 5 | 3 |
| Overall Study | Other | 2 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Persistent Hyperglycemia | 2 | 2 | 5 | 1 | 2 | 5 |
| Overall Study | Physician Decision | 1 | 0 | 1 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 5 | 2 | 2 | 1 | 3 |
Baseline characteristics
| Characteristic | INT131 Besylate 0.5 mg | Total | Placebo | Pioglitazone HCl 45 mg | INT131 Besylate 3 mg | INT131 Besylate 2 mg | INT131 Besylate 1 mg |
|---|---|---|---|---|---|---|---|
| Age Continuous | 54.9 years STANDARD_DEVIATION 8.48 | 55.8 years STANDARD_DEVIATION 9.5 | 55.3 years STANDARD_DEVIATION 10.93 | 55.8 years STANDARD_DEVIATION 10.4 | 54.8 years STANDARD_DEVIATION 9.76 | 56.1 years STANDARD_DEVIATION 7.98 | 58.0 years STANDARD_DEVIATION 9.18 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 180 Participants | 31 Participants | 28 Participants | 32 Participants | 29 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 186 Participants | 30 Participants | 32 Participants | 29 Participants | 34 Participants | 30 Participants |
| Hemoglobin A1c | 8.3 Percent STANDARD_DEVIATION 0.76 | 8.3 Percent STANDARD_DEVIATION 0.72 | 8.4 Percent STANDARD_DEVIATION 0.8 | 8.2 Percent STANDARD_DEVIATION 0.67 | 8.3 Percent STANDARD_DEVIATION 0.65 | 8.5 Percent STANDARD_DEVIATION 0.69 | 8.3 Percent STANDARD_DEVIATION 0.71 |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 36 Participants | 7 Participants | 5 Participants | 5 Participants | 6 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 42 Participants | 6 Participants | 9 Participants | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 46 Participants | 280 Participants | 46 Participants | 44 Participants | 49 Participants | 45 Participants | 50 Participants |
| Region of Enrollment Mexico | 9 participants | 61 participants | 12 participants | 9 participants | 9 participants | 11 participants | 11 participants |
| Region of Enrollment United States | 51 participants | 305 participants | 49 participants | 51 participants | 52 participants | 52 participants | 50 participants |
| Sex: Female, Male Female | 24 Participants | 170 Participants | 28 Participants | 32 Participants | 25 Participants | 32 Participants | 29 Participants |
| Sex: Female, Male Male | 36 Participants | 196 Participants | 33 Participants | 28 Participants | 36 Participants | 31 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 60 | 37 / 61 | 37 / 63 | 35 / 61 | 34 / 60 | 24 / 61 |
| serious Total, serious adverse events | 1 / 60 | 1 / 61 | 2 / 63 | 0 / 61 | 4 / 60 | 4 / 61 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward
HbA1c is measured as percent. Thus this change from baseline reflects the week 24 HbA1c percent minus the Week 0 HbA1c percent
Time frame: Weeks 0-24
Population: Randomized subjects who took at least 1 dose of double blind treatment. To be included in analysis of change from baseline to week 24 with last observation carried forward, subjects must have had baseline measurement and at least 1 post baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INT131 Besylate 0.5 mg | Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward | -0.3 Percernt | Standard Deviation 0.86 |
| INT131 Besylate 1 mg | Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward | -0.6 Percernt | Standard Deviation 0.72 |
| INT131 Besylate 2 mg | Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward | -0.9 Percernt | Standard Deviation 0.97 |
| INT131 Besylate 3 mg | Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward | -1.0 Percernt | Standard Deviation 0.8 |
| Pioglitazone HCl 45 mg | Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward | -0.9 Percernt | Standard Deviation 0.94 |
| Placebo | Change From Baseline in Hemoglobin A1c (HBA1c) at Week 24 With Last Observation Carried Forward | -0.1 Percernt | Standard Deviation 0.87 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward.
The change from baseline reflects the Week 24 FPG minus the Week 0 FPG with last observation carried forward.
Time frame: Weeks 0-24
Population: Randomized subjects who took at least 1 dose of double blind treatment. To be included in analysis of change from baseline to week 24 with last observation carried forward, subjects must have had baseline measurement and at least 1 post baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| INT131 Besylate 0.5 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward. | -0.3 mg/dL | Standard Deviation 58.73 |
| INT131 Besylate 1 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward. | -14.6 mg/dL | Standard Deviation 48.53 |
| INT131 Besylate 2 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward. | -28.9 mg/dL | Standard Deviation 44.2 |
| INT131 Besylate 3 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward. | -26.9 mg/dL | Standard Deviation 37.23 |
| Pioglitazone HCl 45 mg | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward. | -33.2 mg/dL | Standard Deviation 37.17 |
| Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 With Last Observation Carried Forward. | 4.6 mg/dL | Standard Deviation 41.71 |