Clinical trial NCT03335371: Evaluation of TTP399 in Patients With Type 1 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: vTv Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2017-11-07
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
timeFrame: Baseline (Day 1) to Week 13
measure: Sentinel - Area Under the Concentration Time Curve (AUC)
timeFrame: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.
measure: Sentinel - Maximum Drug Concentration (Cmax)
timeFrame: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.
measure: Sentinel - Time to Maximum Concentration (Tmax)
timeFrame: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.
Secondary outcomes:
measure: Percent Change From Baseline Time in Target Glycemic Range (70-180 mg/dL)
timeFrame: Baseline (Day 1) to Week 12
measure: Percent Change From Baseline Time in Hypoglycemia (< 54 mg/dL)
timeFrame: Baseline (Day 1) to Week 12
measure: Percent Change From Baseline Time in Hypoglycemia (< 70 mg/dL)
timeFrame: Baseline (Day 1) to Week 12
measure: Percent Change From Baseline Time in Hyperglycemia (>180 mg/dL)
timeFrame: Baseline (Day 1) to Week 12
measure: Percent Change From Baseline Time in Hyperglycemia (>250 mg/dL)
timeFrame: Baseline (Day 1) to Week 12
measure: Percent Change From Baseline in Total Daily Insulin Use
timeFrame: Baseline (Day 1) to Week 12
measure: Change From Baseline in Bolus Insulin Use
timeFrame: Baseline (Day 1) to Week 12
measure: Change From Baseline in Basal Insulin Use
timeFrame: Baseline (Day 1) to Week 12
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: USC Westside Center for Diabetes
state: California
city: Escondido
country: United States
facility: AMCR Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Barbara Davis Center
state: Colorado
city: Atlanta
country: United States
facility: Atlanta Diabetes Associate
state: Georgia
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes Center
state: Idaho
city: West Des Moines
country: United States
facility: Iowa Diabetes Research
state: Iowa
city: Asheville
country: United States
facility: Mountain Diabetes and Endocrine Center
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Diabetes Care Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Diabetes Research Clinic
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes & Endocrinology Consultants
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest
state: North Carolina
city: Norman
country: United States
facility: Intend Research
state: Oklahoma
city: Dallas
country: United States
facility: Dallas Diabetes Research Center
state: Texas
city: Seattle
country: United States
facility: University of Washington Medicine Diabetes Institute
state: Washington
Study officials:
affiliation: vTv Therapeutics, LLC
name: Carmen Valcarce, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Klein KR, Freeman JLR, Dunn I, Dvergsten C, Kirkman MS, Buse JB, Valcarce C; SimpliciT1 research group. The SimpliciT1 Study: A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Adaptive Study of TTP399, a Hepatoselective Glucokinase Activator, for Adjunctive Treatment of Type 1 Diabetes. Diabetes Care. 2021 Apr;44(4):960-968. doi: 10.2337/dc20-2684. Epub 2021 Feb 23.