Evaluation of TTP399 in Patients With Type 1 Diabetes | NCT03335371

NCT03335371

ID	Type	Description	Link
JDRF#2-IND-2018-500	Other Identifier	JDRF International

Status Module

Sponsor/Collaborators Module

Name	Class
Juvenile Diabetes Research Foundation	OTHER

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
TTP399 400 mg	Experimental		Drug: TTP399
Placebo	Placebo Comparator		Drug: Placebo Oral Tablet

Name	Type	Description	Arm Group Labels	Other Names
TTP399	Drug	Phase 1: Participants will receive TTP399 administered orally up to 1200 mg taken once daily for 7 days	TTP399 400 mg

Outcomes Module

Primary Outcomes

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 Outcomes

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)

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Carmen Valcarce, Ph.D.	vTv Therapeutics, LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
USC Westside Center for Diabetes		Beverly Hills	California	90211	United States
AMCR Institute

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33622669	Derived	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.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sentinels	Sentinel: Participants who received TTP399 400 mg administered orally once daily for 1 week per dose level. Period 1: 400 mg TTP399 administered Period 2: 800 mg TTP399 administered Period 3: 1200 mg TTP399 administered
FG001	Part 1 TTP399 800 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 8, 2019	Nov 23, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

To evaluate the change from baseline time in hypoglycemia (< 54 mg/dL)

Sentinel participants were the same participants throughout the dose levels. Part 1 is the full analysis set. Part 2 is all randomized subjects who received at least 1 dose of the investigational product.

Arm/Group Information

ID	Title	Description
BG000	Sentinel	Sentinel: Participants who received TTP399 400 mg, 800 mg, and 1200 mg administered orally once daily for 1 week per dose level.
BG001	Part 1 TTP399 800 mg	TTP399 Part 1: Participants who received TTP399 800 mg administered orally once daily for 12 weeks with a 1-week follow-up after the last dose was administered.
BG002	Part 1 Placebo	Placebo Part 1: Participants who received placebo tablets administered orally once daily for 12 weeks with a 1-week follow-up after the last dose was administered.
BG003	Part 2 TTP399 800 mg	TTP399 Part 2: Participants who received TTP399 800 mg administered orally once daily for 12 weeks with a 1-week follow-up after the last dose was administered.
BG004	Part 2 Placebo	Placebo Part 2: Participants who received placebo tablets administered orally once daily for 12 weeks with a 1-week follow-up after the last dose was administered.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00032± 7.4 BG00138± 15.71 BG00247± 10.10 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0003 BG0015 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

BMI

Mean

Standard Deviation

kg/m2

Title

Denominators

Categories

Title	Measurements
	BG00024± 3 BG00128± 3.30 BG002

Glycosylated hemoglobin (HbA1c)

Mean

Standard Deviation

Percent HbA1c in blood

Title

Denominators

Categories

Title	Measurements
	BG0006.9± 0.7 BG0017.20± 0.42 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

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

Posted

Least Squares Mean

Standard Error

percent change

Baseline (Day 1) to Week 13

ID	Title	Description
OG000	Part 1 Placebo	Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks
OG001	Part 1 TTP399 800 mg	TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
OG002	Part 2 Placebo	Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks
OG003	Part 2 TTP399 800 mg	TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks

Units	Counts
Participants	OG00011 OG0018 OG00245 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.08± 0.2 OG001-0.60± 0.2 OG0020.07± 0.06 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG002 OG003		ANCOVA		<0.0001		Mean Difference (Final Values)	-0.21	Standard Deviation	0.087	2-Sided	95	-0.39	-0.04					Superiority

Primary

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.

Posted

Mean

Standard Deviation

ng*h/mL

Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.

ID	Title	Description
OG000	Sentinel 400 mg	Sentinel: Participants who received TTP399 400 mg administered orally once daily for 1 week per dose level.
OG001	Sentinel 800 mg	Sentinel: Participants who received TTP399 800 mg administered orally once daily for 1 week per dose level.
OG002	Sentinel 1200 mg	Sentinel: Participants who received TTP399 1200 mg administered orally once daily for 1 week per dose level.

Units	Counts
Participants	OG000

Primary

Sentinel - Maximum Drug Concentration (Cmax)

Posted

Mean

Standard Deviation

ng/mL

Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.

ID	Title	Description
OG000	Sentinel 400 mg	Sentinel: Participants who received TTP399 400 mg administered orally once daily for 1 week per dose level.
OG001	Sentinel 800 mg	Sentinel: Participants who received TTP399 800 mg administered orally once daily for 1 week per dose level.
OG002	Sentinel 1200 mg	Sentinel: Participants who received TTP399 1200 mg administered orally once daily for 1 week per dose level.

Units	Counts
Participants	OG000

Secondary

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)

Part 1 is the full analysis set. Part 2 is all randomized subjects who received at least 1 dose of the investigational product.

Posted

Mean

Standard Deviation

percent change

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Part 1 Placebo	Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks
OG001	Part 1 TTP399 800 mg	TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
OG002	Part 2 Placebo	Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks
OG003	Part 2 TTP399 800 mg	TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks

Secondary

Percent Change From Baseline Time in Hypoglycemia (< 54 mg/dL)

To evaluate the change from baseline time in hypoglycemia (< 54 mg/dL)

Part 1 is the full analysis set. Part 2 is all randomized subjects who received at least 1 dose of the investigational product.

Posted

Median

Full Range

percent change

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Part 1 Placebo	Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks
OG001	Part 1 TTP399 800 mg	TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
OG002	Part 2 Placebo	Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks
OG003	Part 2 TTP399 800 mg	TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks

Secondary

Percent Change From Baseline Time in Hypoglycemia (< 70 mg/dL)

To evaluate the change from baseline time in hypoglycemia (< 70 mg/dL)

Posted

Mean

Standard Deviation

percent change

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Part 1 Placebo	Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks
OG001	Part 1 TTP399 800 mg	TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
OG002	Part 2 Placebo	Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks
OG003	Part 2 TTP399 800 mg	TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks

Units	Counts

Secondary

Percent Change From Baseline Time in Hyperglycemia (>180 mg/dL)

To evaluate the change from baseline time in hypoglycemia (>180 mg/dL)

Part 1 is the full analysis set. Part 2 is all randomized subjects who received at least 1 dose of the investigational product.

Posted

Mean

Standard Deviation

percent change

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Part 1 Placebo	Placebo Part 1: Participants will receive Placebo oral tablets for 12 week
OG001	Part 1 TTP399 800 mg	TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
OG002	Part 2 Placebo	Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks
OG003	Part 2 TTP399 800 mg	TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks

Secondary

Percent Change From Baseline Time in Hyperglycemia (>250 mg/dL)

To evaluate the change from baseline time in hypoglycemia (>250 mg/dL)

Time in hypoglycemia >250mg/dL was only evaluated in Part 2 of the study. Part 2 is all randomized subjects who received at least 1 dose of the investigational product.

Posted

Mean

Standard Deviation

percent change

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Part 2 Placebo	Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks
OG001	Part 2 TTP399 800 mg	TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Total Daily Insulin Use

To evaluate the percent change from baseline in total daily insulin use at week 12.

Part 1 is the full analysis set. Part 2 is all randomized subjects who received at least 1 dose of the investigational product.

Posted

Mean

Standard Deviation

percent change

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Part 1 Placebo	Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks
OG001	Part 1 TTP399 800 mg	TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
OG002	Part 2 Placebo	Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks
OG003	Part 2 TTP399 800 mg	TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks

Secondary

Change From Baseline in Bolus Insulin Use

To evaluate the change from baseline in bolus insulin use

Posted

Mean

Standard Deviation

units/kg/day

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Part 1 Placebo	Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks
OG001	Part 1 TTP399 800 mg	TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
OG002	Part 2 Placebo	Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks
OG003	Part 2 TTP399 800 mg	TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks

Units	Counts

Secondary

Change From Baseline in Basal Insulin Use

To evaluate the change from baseline in basal insulin use

Posted

Mean

Standard Deviation

units/kg/day

Baseline (Day 1) to Week 12

ID	Title	Description
OG000	Part 1 Placebo	Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks
OG001	Part 1 TTP399 800 mg	TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
OG002	Part 2 Placebo	Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks
OG003	Part 2 TTP399 800 mg	TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks

Units	Counts

Primary

Sentinel - Time to Maximum Concentration (Tmax)

Posted

Median

Full Range

hour

Predose, 60, 90, 120, 150, 180, 240, 360 (6hr) and 540min (9hr) after dosing.

ID	Title	Description
OG000	Sentinel 400 mg	Sentinel: Participants who received TTP399 400 mg administered orally once daily for 1 week per dose level.
OG001	Sentinel 800 mg	Sentinel: Participants who received TTP399 800 mg administered orally once daily for 1 week per dose level.
OG002	Sentinel 1200 mg	Sentinel: Participants who received TTP399 1200 mg administered orally once daily for 1 week per dose level.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sentinel 400 mg	Sentinel: Participants who received TTP399 400 mg administered orally once daily for 1 week per dose level.	5	0	5	2	5
EG001	Sentinel 800 mg	Sentinel: Participants who received TTP399 800 mg administered orally once daily for 1 week per dose level.	5	0	5	1	5
EG002	Sentinel 1200 mg	Sentinel: Participants who received TTP399 1200 mg administered orally once daily for 1 week per dose level.	5	0	5	2	5
EG003	Placebo (Part 1 and Part 2)	Placebo Part 1 and Part 2: Participants will receive Placebo oral tablets for 12 weeks	56	1	56	32	56
EG004	TTP399 800 mg (Part 1 and Part 2)	TTP399 Part 1 and TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	49	1	49	25	49

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Coronary Artery Disease	Cardiac disorders		Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG0031 events1 affected56 at risk EG0040 events0 affected49 at risk
Non-Cardiac Chest Pain	General disorders		Systematic Assessment		EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG0036 events6 affected56 at risk EG0047 events7 affected49 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG003
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG003
Ear infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG003
Hypoglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 events2 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG003
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected5 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG003
Hypocalcemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected5 at risk EG003
Right Eye Discomfort	Eye disorders	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected5 at risk EG003
Headache	Nervous system disorders	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected5 at risk EG003

First MCP Posted Date

ID	Term
D003922	Diabetes Mellitus, Type 1

Ancestor Terms

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
C000654432	TTP399

Units	Counts
Participants	OG00011 OG0018 OG00243 OG00338

Units	Counts
Participants	OG00011 OG0018 OG00243 OG00338

Units	Counts
Participants	OG00011 OG0018 OG00243 OG00338

Units	Counts
Participants	OG00011 OG0018 OG00243 OG00338

EG0041 events1 affected49 at risk

EG0043 events3 affected49 at risk

EG0040 events0 affected49 at risk

EG0043 events3 affected49 at risk

EG00412 events5 affected49 at risk

EG0043 events3 affected49 at risk

EG0042 events2 affected49 at risk

EG0040 events0 affected49 at risk