Trial Outcomes & Findings for Evaluation of TTP399 in Patients With Type 1 Diabetes (NCT NCT03335371)

NCT ID: NCT03335371

Last Updated: 2023-07-03

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 115 participants
• Primary outcome timeframe: Baseline (Day 1) to Week 13
• Results posted on: 2023-07-03

Participant Flow

A total of 110 participants were randomized to the study groups: Sentinel, Part 1, and Part 2. Sentinel participants were the same participants throughout the dose levels.

Participant milestones

Measure	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	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.	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.	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.	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.
Overall Study STARTED	5	9	11	40	45
Overall Study COMPLETED	5	9	10	40	43
Overall Study NOT COMPLETED	0	0	1	0	2

Reasons for withdrawal

Measure	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	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.	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.	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.	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.
Overall Study Lost to Follow-up	0	0	0	0	1
Overall Study Withdrawal by Subject	0	0	0	0	1
Overall Study Randomization Error	0	0	1	0	0

Baseline Characteristics

Evaluation of TTP399 in Patients With Type 1 Diabetes

Baseline characteristics by cohort

Measure	Sentinel n=5 Participants Sentinel: Participants who received TTP399 400 mg, 800 mg, and 1200 mg administered orally once daily for 1 week per dose level.	Part 1 TTP399 800 mg n=8 Participants 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.	Part 1 Placebo n=11 Participants 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.	Part 2 TTP399 800 mg n=40 Participants 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.	Part 2 Placebo n=45 Participants 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.	Total n=109 Participants Total of all reporting groups
Age, Continuous	32 years STANDARD_DEVIATION 7.4 • n=5 Participants	38 years STANDARD_DEVIATION 15.71 • n=7 Participants	47 years STANDARD_DEVIATION 10.10 • n=5 Participants	43 years STANDARD_DEVIATION 15.26 • n=4 Participants	42 years STANDARD_DEVIATION 13.26 • n=21 Participants	42.5 years STANDARD_DEVIATION 13.76 • n=10 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	15 Participants n=4 Participants	25 Participants n=21 Participants	56 Participants n=10 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	25 Participants n=4 Participants	20 Participants n=21 Participants	53 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	39 Participants n=4 Participants	43 Participants n=21 Participants	106 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants	38 Participants n=4 Participants	43 Participants n=21 Participants	104 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
BMI	24 kg/m2 STANDARD_DEVIATION 3 • n=5 Participants	28 kg/m2 STANDARD_DEVIATION 3.30 • n=7 Participants	29 kg/m2 STANDARD_DEVIATION 4.13 • n=5 Participants	28 kg/m2 STANDARD_DEVIATION 4.16 • n=4 Participants	28 kg/m2 STANDARD_DEVIATION 3.76 • n=21 Participants	28 kg/m2 STANDARD_DEVIATION 3.8 • n=10 Participants
Glycosylated hemoglobin (HbA1c)	6.9 Percent HbA1c in blood STANDARD_DEVIATION 0.7 • n=5 Participants	7.20 Percent HbA1c in blood STANDARD_DEVIATION 0.42 • n=7 Participants	7.36 Percent HbA1c in blood STANDARD_DEVIATION 0.41 • n=5 Participants	7.66 Percent HbA1c in blood STANDARD_DEVIATION 0.56 • n=4 Participants	7.52 Percent HbA1c in blood STANDARD_DEVIATION 0.59 • n=21 Participants	7.45 Percent HbA1c in blood STANDARD_DEVIATION 0.7 • n=10 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to Week 13

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

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.

Outcome measures

Measure	Part 1 Placebo n=11 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=8 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=45 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg n=40 Participants TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Percent Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 12	0.08 percent change Standard Error 0.2	-0.60 percent change Standard Error 0.2	0.07 percent change Standard Error 0.06	-0.14 percent change Standard Error 0.06

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Part 1 Placebo n=5 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=5 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=5 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Sentinel - Area Under the Concentration Time Curve (AUC)	1778 ng*h/mL Standard Deviation 992	1482 ng*h/mL Standard Deviation 341	4848 ng*h/mL Standard Deviation 2663	—

PRIMARY outcome

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

Outcome measures

Measure	Part 1 Placebo n=5 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=5 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=5 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Sentinel - Maximum Drug Concentration (Cmax)	645 ng/mL Standard Deviation 219	813 ng/mL Standard Deviation 129	2038 ng/mL Standard Deviation 1415	—

PRIMARY outcome

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

Outcome measures

Measure	Part 1 Placebo n=5 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=5 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=5 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Sentinel - Time to Maximum Concentration (Tmax)	1.5 hour Interval 1.5 to 2.5	1.5 hour Interval 1.5 to 2.0	2.5 hour Interval 1.5 to 3.0	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

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

To evaluate the change from baseline time in target range (24 hour)

Outcome measures

Measure	Part 1 Placebo n=11 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=8 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=43 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg n=38 Participants TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Percent Change From Baseline Time in Target Glycemic Range (70-180 mg/dL)	-8 percent change Standard Deviation 10	-3 percent change Standard Deviation 8	-7 percent change Standard Deviation 14.0	0.50 percent change Standard Deviation 16

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

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

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

Outcome measures

Measure	Part 1 Placebo n=11 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=8 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=43 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg n=38 Participants TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Percent Change From Baseline Time in Hypoglycemia (< 54 mg/dL)	-0.1 percent change Interval -2.0 to 2.0	-0.1 percent change Interval -3.0 to 0.0	-0.5 percent change Interval -8.0 to 8.0	-0.5 percent change Interval -8.0 to 22.0

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

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

Outcome measures

Measure	Part 1 Placebo n=11 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=8 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=43 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg n=38 Participants TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Percent Change From Baseline Time in Hypoglycemia (< 70 mg/dL)	-1 percent change Standard Deviation 3	-1 percent change Standard Deviation 3	-2 percent change Standard Deviation 5	-2 percent change Standard Deviation 8

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

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

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

Outcome measures

Measure	Part 1 Placebo n=11 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=8 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=43 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg n=38 Participants TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Percent Change From Baseline Time in Hyperglycemia (>180 mg/dL)	9 percent change Standard Deviation 12	5 percent change Standard Deviation 8	10 percent change Standard Deviation 17	1 percent change Standard Deviation 18

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

Population: 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.

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

Outcome measures

Measure	Part 1 Placebo n=43 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=38 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Percent Change From Baseline Time in Hyperglycemia (>250 mg/dL)	6 percent change Standard Deviation 11	2 percent change Standard Deviation 12	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

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

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

Outcome measures

Measure	Part 1 Placebo n=11 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=8 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=43 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg n=38 Participants TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Percent Change From Baseline in Total Daily Insulin Use	-0.1 percent change Standard Deviation 8.7	-1.7 percent change Standard Deviation 14.7	-1.6 percent change Standard Deviation 16	-7.6 percent change Standard Deviation 10.1

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

To evaluate the change from baseline in bolus insulin use

Outcome measures

Measure	Part 1 Placebo n=11 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=8 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=43 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg n=38 Participants TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Change From Baseline in Bolus Insulin Use	-5.9 units/kg/day Standard Deviation 17.5	-1 units/kg/day Standard Deviation 31.8	-3.9 units/kg/day Standard Deviation 28.4	-8.4 units/kg/day Standard Deviation 22.7

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 12

To evaluate the change from baseline in basal insulin use

Outcome measures

Measure	Part 1 Placebo n=11 Participants Placebo Part 1: Participants will receive Placebo oral tablets for 12 weeks	Part 1 TTP399 800 mg n=8 Participants TTP399 Part 1: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks	Part 2 Placebo n=43 Participants Placebo Part 2: Participants will receive Placebo oral tablets for 12 weeks	Part 2 TTP399 800 mg n=38 Participants TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Change From Baseline in Basal Insulin Use	4.4 units/kg/day Standard Deviation 7.7	-2.3 units/kg/day Standard Deviation 10.3	-0.5 units/kg/day Standard Deviation 11.6	-5.4 units/kg/day Standard Deviation 7.1

Adverse Events

Sentinel 400 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Sentinel 800 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Sentinel 1200 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo (Part 1 and Part 2)

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

TTP399 800 mg (Part 1 and Part 2)

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sentinel 400 mg n=5 participants at risk Sentinel: Participants who received TTP399 400 mg administered orally once daily for 1 week per dose level.	Sentinel 800 mg n=5 participants at risk Sentinel: Participants who received TTP399 800 mg administered orally once daily for 1 week per dose level.	Sentinel 1200 mg n=5 participants at risk Sentinel: Participants who received TTP399 1200 mg administered orally once daily for 1 week per dose level.	Placebo (Part 1 and Part 2) n=56 participants at risk Placebo Part 1 and Part 2: Participants will receive Placebo oral tablets for 12 weeks	TTP399 800 mg (Part 1 and Part 2) n=49 participants at risk TTP399 Part 1 and TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Cardiac disorders Coronary Artery Disease	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	1.8% 1/56 • Number of events 1 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/49 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
General disorders Non-Cardiac Chest Pain	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/56 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	2.0% 1/49 • Number of events 1 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.

Other adverse events

Measure	Sentinel 400 mg n=5 participants at risk Sentinel: Participants who received TTP399 400 mg administered orally once daily for 1 week per dose level.	Sentinel 800 mg n=5 participants at risk Sentinel: Participants who received TTP399 800 mg administered orally once daily for 1 week per dose level.	Sentinel 1200 mg n=5 participants at risk Sentinel: Participants who received TTP399 1200 mg administered orally once daily for 1 week per dose level.	Placebo (Part 1 and Part 2) n=56 participants at risk Placebo Part 1 and Part 2: Participants will receive Placebo oral tablets for 12 weeks	TTP399 800 mg (Part 1 and Part 2) n=49 participants at risk TTP399 Part 1 and TTP399 Part 2: Participants will receive TTP399 administered orally 800 mg taken once daily for 12 weeks
Infections and infestations Upper respiratory tract infection	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	10.7% 6/56 • Number of events 6 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	14.3% 7/49 • Number of events 7 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Infections and infestations Nasopharyngitis	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	5.4% 3/56 • Number of events 3 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	6.1% 3/49 • Number of events 3 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Infections and infestations Urinary tract infection	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	7.1% 4/56 • Number of events 4 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/49 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Infections and infestations Ear infection	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/56 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	6.1% 3/49 • Number of events 3 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Metabolism and nutrition disorders Hypoglycemia	40.0% 2/5 • Number of events 2 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	16.1% 9/56 • Number of events 27 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	10.2% 5/49 • Number of events 12 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Gastrointestinal disorders Nausea	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	20.0% 1/5 • Number of events 1 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	7.1% 4/56 • Number of events 4 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	6.1% 3/49 • Number of events 3 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	5.4% 3/56 • Number of events 3 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	4.1% 2/49 • Number of events 2 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	5.4% 3/56 • Number of events 3 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	4.1% 2/49 • Number of events 2 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	20.0% 1/5 • Number of events 1 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/56 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/49 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Eye disorders Right Eye Discomfort	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	20.0% 1/5 • Number of events 1 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/56 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/49 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.
Nervous system disorders Headache	20.0% 1/5 • Number of events 1 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/5 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	3.6% 2/56 • Number of events 2 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.	0.00% 0/49 • 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. The safety analysis set includes all patients who received at least one dose of study medication. Sentinel participants were the same participants throughout the dose levels.

Additional Information

Study Director

vTv Therapeutics LLC

Phone: 336-841-0300

Email: clinicaltrials@vtvtherapeutics.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60