Diabetes Mellitus, Type 1Phase 1/2SimpliciT1NCT03335371

Evaluation of TTP399 in Patients With Type 1 Diabetes

A Phase 1/2 study testing TTP399 in people with Diabetes Mellitus, Type 1, run by vTv Therapeutics at 15 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Diabetes Mellitus, Type 1
What is being tested?: TTP399
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 115 participants
Where: 15 sitesUnited States
Study dates: 25 Oct 2017to 6 Jan 2020
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 14Show fewer

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

Trial locations and contacts

15 sites in 1 country.

City, postcode or hospital

15 sites in 1 country

United States15 sites

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

Other trials in United States

About this study

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

Conditions: Diabetes Mellitus, Type 1
Being tested: TTP399, Placebo Oral Tablet
Medical subject headings: Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TTP399Drug
Phase 1: Participants will receive TTP399 administered orally up to 1200 mg taken once daily for 7 days
TTP399Drug
Phase 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Placebo Oral TabletDrug
Phase 2: Participants will receive Placebo oral tablets for 12 weeks

Study groups in NCT03335371
Study group	Role	What they receive
TTP399 400 mg	Experimental	Not described Receives: Drug: TTP399
Placebo	Placebo comparator	Not described Receives: Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.
Sentinel - Maximum Drug Concentration (Cmax)
Measured: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.
Sentinel - Time to Maximum Concentration (Tmax)
Measured: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.

Secondary outcomes (8)

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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: Baseline (Day 1) to Week 12
Change From Baseline in Bolus Insulin Use
To evaluate the change from baseline in bolus insulin use
Measured: Baseline (Day 1) to Week 12
Change From Baseline in Basal Insulin Use
To evaluate the change from baseline in basal insulin use
Measured: Baseline (Day 1) to Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Oct 20176 Jan 2020

First posted7 Nov 2017
Study start25 Oct 2017
Primary completion20 Dec 2019
Study completion6 Jan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 115 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03335371
Sponsor's protocol ID: TTP399-203
Other IDs: JDRF#2-IND-2018-500
Acronym: SimpliciT1
Status last verified: Jun 2023
First submitted: 31 Oct 2017
Last updated: 3 Jul 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 33622669

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03335371
Acronym / sponsor ID: SimpliciT1 / TTP399-203
Conditions: Diabetes Mellitus, Type 1
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 115 participants (actual)
Lead sponsor: vTv TherapeuticsIndustry (pharma, biotech, devices)
Collaborators: Juvenile Diabetes Research Foundation
Study start: 25 Oct 2017 (actual)
Primary completion: 20 Dec 2019 (actual)
Study completion: 6 Jan 2020 (actual)
First posted: 7 Nov 2017 (actual)
Results: Posted 3 Jul 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
TTP399 400 mg	Experimental	Drug: TTP399
Placebo	Placebo comparator	Drug: Placebo Oral Tablet

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (14 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TTP399Phase 1: Participants will receive TTP399 administered orally up to 1200 mg taken once daily for 7 days	Drug	TTP399 400 mg
TTP399Phase 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Drug	TTP399 400 mg
Placebo Oral TabletPhase 2: Participants will receive Placebo oral tablets for 12 weeks	Drug	Placebo

Primary outcome

Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12
Time frame: Baseline (Day 1) to Week 13
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.
Sentinel - Area Under the Concentration Time Curve (AUC)
Time frame: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.
AUC for Day 1 per dose level (400 mg, 800 mg, and 1200 mg) is AUC from 0 to 9 hours.
Sentinel - Maximum Drug Concentration (Cmax)
Time frame: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.
Sentinel - Time to Maximum Concentration (Tmax)
Time frame: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.

8 secondary outcomes

Percent Change From Baseline Time in Target Glycemic Range (70-180 mg/dL)
Time frame: Baseline (Day 1) to Week 12
Percent Change From Baseline Time in Hypoglycemia (< 54 mg/dL)
Time frame: Baseline (Day 1) to Week 12
Percent Change From Baseline Time in Hypoglycemia (< 70 mg/dL)
Time frame: Baseline (Day 1) to Week 12
Percent Change From Baseline Time in Hyperglycemia (>180 mg/dL)
Time frame: Baseline (Day 1) to Week 12
Percent Change From Baseline Time in Hyperglycemia (>250 mg/dL)
Time frame: Baseline (Day 1) to Week 12
Percent Change From Baseline in Total Daily Insulin Use
Time frame: Baseline (Day 1) to Week 12
Change From Baseline in Bolus Insulin Use
Time frame: Baseline (Day 1) to Week 12
Change From Baseline in Basal Insulin Use
Time frame: Baseline (Day 1) to Week 12

Results and safety

Results posted to the registry on 3 Jul 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sentinels	5	5
Part 1 TTP399 800 mg	9	9
Part 1 Placebo	11	10
Part 2 TTP399 800 mg	40	40
Part 2 Placebo	45	43

Primary outcome: Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12

Time frame: Baseline (Day 1) to Week 13. Least squares mean (Standard Error). Unit: percent change

Measure	Part 1 Placebo n = 11	Part 1 TTP399 800 mg n = 8	Part 2 Placebo n = 45	Part 2 TTP399 800 mg n = 40
Value	0.08 (0.2)	-0.60 (0.2)	0.07 (0.06)	-0.14 (0.06)

Part 2 Placebo vs Part 2 TTP399 800 mg: Mean Difference (Final Values): -0.21 (95% CI -0.39 to -0.04), p <0.0001, ANCOVA

Population analysed: Part 1 and Part 2 populations are the full analysis of randomized subjects. Sentinel participants were not evaluated for a change in HbA1C.

Primary outcome: Sentinel - Area Under the Concentration Time Curve (AUC)

Time frame: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.. Mean (Standard Deviation). Unit: ng*h/mL

Measure	Sentinel 400 mg n = 5	Sentinel 800 mg n = 5	Sentinel 1200 mg n = 5
Value	1778 (992)	1482 (341)	4848 (2663)

Primary outcome: Sentinel - Maximum Drug Concentration (Cmax)

Time frame: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.. Mean (Standard Deviation). Unit: ng/mL

Measure	Sentinel 400 mg n = 5	Sentinel 800 mg n = 5	Sentinel 1200 mg n = 5
Value	645 (219)	813 (129)	2038 (1415)

Primary outcome: Sentinel - Time to Maximum Concentration (Tmax)

Time frame: Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.. Median (Full Range). Unit: hour

Measure	Sentinel 400 mg n = 5	Sentinel 800 mg n = 5	Sentinel 1200 mg n = 5
Value	1.5 (1.5 to 2.5)	1.5 (1.5 to 2.0)	2.5 (1.5 to 3.0)

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment-emergent adverse events were those reported at baseline up to 12 weeks (±3) days after the last dose. Unresolved AEs were followed up by the investigator for as long as medically indicated. Sentinel group reported at baseline up to 28 days after the last dose.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sentinel 400 mg	0 of 5 (0%)	2 of 5 (40%)	0 of 5
Sentinel 800 mg	0 of 5 (0%)	1 of 5 (20%)	0 of 5
Sentinel 1200 mg	0 of 5 (0%)	2 of 5 (40%)	0 of 5
Placebo (Part 1 and Part 2)	1 of 56 (1.8%)	32 of 56 (57.1%)	0 of 56
TTP399 800 mg (Part 1 and Part 2)	1 of 49 (2%)	25 of 49 (51%)	0 of 49

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33622669Klein 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Carmen Valcarce, Ph.D. study director

vTv Therapeutics, LLC

15 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TTP399 in people with Diabetes Mellitus, Type 1, run by vTv Therapeutics at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12 (time frame: Baseline (Day 1) to Week 13). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03335371, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2023.