Evaluation of TTP399 in Patients With Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of TTP399 in Type 1 diabetics. This study will be in 2 phases: phase 1 will evaluate the safety of different TTP399 dosage regimens over 1 week of daily dosing. Phase 2 will evaluate the safety and efficacy of a TTP399 dosing regimen over 12 weeks of daily dosing.

Official Title
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A Multi-Center, Randomized, Double-Blind, Parallel-Group, Multiple-Dose, Adaptive Study Assessing the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of TTP399 in With Adult Patients Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: TTP399
* Drug: TTP399
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: People diagnosed with T1DM, confirmed diagnosis prior to 40 years of age and a diagnosed for minimum of 1 year. Type 1 diabetics using either continuous subcutaneous insulin infusion (with lispro or aspart) or multiple daily doses of insulin Willing to use adequate contraception No major surgeries or significant injuries within the past year and without an active infection. Exclusion Criteria: Diagnosis of T2DM, severely uncontrolled T1DM, maturity-onset diabetes of the young, insulin-requiring T2DM, other unusual or rare forms of diabetes mellitus, diabetes resulting from a secondary disease Receipt of an investigational product within 30 days of the Screening Visit or any therapeutic protein or antibody within 90 days prior to Screening Visit or any previous treatment with TTP399. Living in the same household or related to another participant in this study. Two severe episodes of hypoglycemia that required assistance by a third party within 3 months of Screening Visit Use of antidiabetic medications other than insulin 3 months prior to Screening Visit, systemic corticosteroids 1 month prior to Screening Visit, weight loss medication 2 weeks prior to Screening Visit, and antipsychotic medications 3 months prior to Screening Visit. Participation in any formal weight loss program or contemplating such therapy during the trial. Recent history of use of non-prescribed controlled substances or illicit drugs. Current alcoholism or a history of excessive alcohol consumption within 2 years prior to screening History or presence of symptomatic autonomic neuropathy or chronic gastrointestinal disease. Personal history of long QT syndrome. Blood donation of approximately 1 pint (500 mL) within 8 weeks before Screening Visit History of hemolytic anemia or chronic transfusion requirement. History of cancer, other than non-melanoma skin cancer or uterine cervical cancer that required therapy in the past 5 years. Breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TTP399 400 mg<br> | Drug: TTP399<br>* Phase 1: Participants will receive TTP399 administered orally up to 1200 mg taken once daily for 7 days<br>Drug: TTP399<br>* Phase 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo Oral Tablet<br>* Phase 2: Participants will receive Placebo oral tablets for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 | To evaluate the change in glycosylated hemoglobin (HbA1C) in Part 1 and Part 2 participants following multiple-day dosing (at 12 weeks) in subjects with T1MD. Sentinel participants were not evaluated for a change in HbA1C. | Baseline (Day 1) to Week 13 | 
| Sentinel - Area Under the Concentration Time Curve (AUC) | AUC for Day 1 per dose level (400 mg, 800 mg, and 1200 mg) is AUC from 0 to 9 hours. | Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing. | 
| Sentinel - Maximum Drug Concentration (Cmax) |  | Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing. | 
| Sentinel - Time to Maximum Concentration (Tmax) |  | Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline Time in Target Glycemic Range (70-180 mg/dL) | To evaluate the change from baseline time in target range (24 hour) | Baseline (Day 1) to Week 12 | 
| Percent Change From Baseline Time in Hypoglycemia (< 54 mg/dL) | To evaluate the change from baseline time in hypoglycemia (< 54 mg/dL) | Baseline (Day 1) to Week 12 | 
| Percent Change From Baseline Time in Hypoglycemia (< 70 mg/dL) | To evaluate the change from baseline time in hypoglycemia (< 70 mg/dL) | Baseline (Day 1) to Week 12 | 
| Percent Change From Baseline Time in Hyperglycemia (>180 mg/dL) | To evaluate the change from baseline time in hypoglycemia (>180 mg/dL) | Baseline (Day 1) to Week 12 | 
| Percent Change From Baseline Time in Hyperglycemia (>250 mg/dL) | To evaluate the change from baseline time in hypoglycemia (>250 mg/dL) | Baseline (Day 1) to Week 12 | 
| Percent Change From Baseline in Total Daily Insulin Use | To evaluate the percent change from baseline in total daily insulin use at week 12. | Baseline (Day 1) to Week 12 | 
| Change From Baseline in Bolus Insulin Use | To evaluate the change from baseline in bolus insulin use | Baseline (Day 1) to Week 12 | 
| Change From Baseline in Basal Insulin Use | To evaluate the change from baseline in basal insulin use | Baseline (Day 1) to Week 12 |