Evaluation of TTP399 in Patients With Type 1 Diabetes (SimpliciT1)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: TTP399; Drug: TTP399; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • USC Westside Center for Diabetes
    • Escondido, California, United States, 92025
      • AMCR Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Barbara Davis Center
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associate
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Diabetes Center
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes Research
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Mountain Diabetes and Endocrine Center
    • Chapel Hill, North Carolina, United States, 27517
      • UNC Diabetes Care Center
    • Durham, North Carolina, United States, 27710
      • Duke University Diabetes Research Clinic
    • Morehead City, North Carolina, United States, 28557
      • Diabetes & Endocrinology Consultants
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington
    • Winston-Salem, North Carolina, United States, 27104
      • Wake Forest
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Intend Research
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Research Center
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington Medicine Diabetes Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: vTv Therapeutics
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Study Director: Carmen Valcarce, Ph.D., vTv Therapeutics, LLC

Publications and helpful links

General Publications

• 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.

Helpful Links

• 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

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2017
• Primary Completion (Actual): December 20, 2019
• Study Completion (Actual): January 6, 2020

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: November 3, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: TTP399-203; JDRF#2-IND-2018-500 (Other Identifier: JDRF International)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No