Trial Outcomes & Findings for A Study to Evaluate the Effects of NST-4016 on QT/Corrected QT (QTc) Interval (NCT NCT03577275)

NCT ID: NCT03577275

Last Updated: 2019-11-04

Results Overview

Electrocardiogram measurement of the maximum absolute change from baseline in Fridericia's correction for QT interval (QTcF)

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 32 participants
• Primary outcome timeframe: 24 hours
• Results posted on: 2019-11-04

Participant Flow

This was a cross over study so 32 subjects each completed 4 treatment arms

Participant milestones

Measure	All Study Participants This was a 4 way crossover study in which all study participants received the following treatments in random order; NST-4016 2000mg: Supratherapeutic dose of NST-4016, NST-4016 600mg: Likely maximum therapeutic dose of NST-4016, Moxifloxacin 400mg: Active comparator with known effect on QT interval, Placebo oral capsule: Placebo for comparison with moxifloxacin and potential NST-4016 effects. There were 12 possible treatment sequences
Overall Study STARTED	32
Overall Study Placebo	32
Overall Study Moxifloxacin 400mg	32
Overall Study NST-4016 600mg	32
Overall Study NST-4016 2000mg	32
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Effects of NST-4016 on QT/Corrected QT (QTc) Interval

Baseline characteristics by cohort

Measure	All Study Participants n=32 Participants All participants were randomized to receive all 4 interventions
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	32 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United Kingdom	32 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: The primary endpoint for this trial was the placebo corrected change from baseline in QTcF. The data presented here are the maximum absolute change from baseline for placebo, moxifloxacin 400mg, NST-4016 600mg and NST-4016 2000mg.

Electrocardiogram measurement of the maximum absolute change from baseline in Fridericia's correction for QT interval (QTcF)

Outcome measures

Measure	Placebo Oral Capsule n=32 Participants Single dose of placebo to match NST-4016 Placebo oral capsule: Placebo for comparison with moxifloxacin and potential NST-4016 effects	Moxifloxacin 400mg n=32 Participants Single 400mg dose of active comparator moxifloxacin (open label) Moxifloxacin 400mg: Active comparator with known effect on QT interval	NST-4016 600mg n=32 Participants Likely therapeutic dose of NST-4016 NST-4016 600mg: Likely maximum therapeutic dose of NST-4016	NST-4016 2000mg n=32 Participants Supratherapeutic dose of NST-4016 NST-4016 2000mg: Supratherapeutic dose of NST-4016
Change From Baseline in Fridericia's Correction for QT Interval (QTcF)	-4.6 msec Standard Error 1.52	11.5 msec Standard Error 0.88	-6.0 msec Standard Error 1.39	-6.1 msec Standard Error 1.42

SECONDARY outcome

Timeframe: 24 hours

Population: maximum values of change in heart rate from baseline over the 24 hours post dose

Electrocardiogram measurement of change from baseline in heart rate (HR) maximum values presented

Outcome measures

Measure	Placebo Oral Capsule n=32 Participants Single dose of placebo to match NST-4016 Placebo oral capsule: Placebo for comparison with moxifloxacin and potential NST-4016 effects	Moxifloxacin 400mg n=32 Participants Single 400mg dose of active comparator moxifloxacin (open label) Moxifloxacin 400mg: Active comparator with known effect on QT interval	NST-4016 600mg n=32 Participants Likely therapeutic dose of NST-4016 NST-4016 600mg: Likely maximum therapeutic dose of NST-4016	NST-4016 2000mg n=32 Participants Supratherapeutic dose of NST-4016 NST-4016 2000mg: Supratherapeutic dose of NST-4016
Change From Baseline in Heart Rate (HR)	9.9 beats per minute Standard Error 0.86	12.2 beats per minute Standard Error 0.85	12.6 beats per minute Standard Error 0.88	15.6 beats per minute Standard Error 0.85

SECONDARY outcome

Timeframe: 24 hours

Population: The largest change in QTcF for each arm during the study is presented below

Electrocardiogram measurement of change from baseline in Fridericia's correction for QT interval (QTcF)

Outcome measures

Measure	Placebo Oral Capsule n=32 Participants Single dose of placebo to match NST-4016 Placebo oral capsule: Placebo for comparison with moxifloxacin and potential NST-4016 effects	Moxifloxacin 400mg n=32 Participants Single 400mg dose of active comparator moxifloxacin (open label) Moxifloxacin 400mg: Active comparator with known effect on QT interval	NST-4016 600mg n=32 Participants Likely therapeutic dose of NST-4016 NST-4016 600mg: Likely maximum therapeutic dose of NST-4016	NST-4016 2000mg n=32 Participants Supratherapeutic dose of NST-4016 NST-4016 2000mg: Supratherapeutic dose of NST-4016
Change From Baseline in Fridericia's Correction for QT Interval (QTcF)	-4.6 msec Standard Error 1.52	11.5 msec Standard Error 0.88	-6.0 msec Standard Error 1.39	-5.7 msec Standard Error 1.39

SECONDARY outcome

Timeframe: 24 hours

Population: maximum change from baseline during the study period is reported

Electrocardiogram measurement of change from baseline in PR interval (PR)

Outcome measures

Measure	Placebo Oral Capsule n=32 Participants Single dose of placebo to match NST-4016 Placebo oral capsule: Placebo for comparison with moxifloxacin and potential NST-4016 effects	Moxifloxacin 400mg n=32 Participants Single 400mg dose of active comparator moxifloxacin (open label) Moxifloxacin 400mg: Active comparator with known effect on QT interval	NST-4016 600mg n=32 Participants Likely therapeutic dose of NST-4016 NST-4016 600mg: Likely maximum therapeutic dose of NST-4016	NST-4016 2000mg n=32 Participants Supratherapeutic dose of NST-4016 NST-4016 2000mg: Supratherapeutic dose of NST-4016
Change From Baseline in PR Interval (PR)	-11.0 msec Standard Error 1.32	-11.9 msec Standard Error 1.30	-11.4 msec Standard Error 1.36	-12.4 msec Standard Error 1.30

SECONDARY outcome

Timeframe: 2 hours

Population: The data presented is from the 2 hour time point corresponding to T max

Electrocardiogram measurement of change from baseline in QRS interval (QRS)

Outcome measures

Measure	Placebo Oral Capsule n=32 Participants Single dose of placebo to match NST-4016 Placebo oral capsule: Placebo for comparison with moxifloxacin and potential NST-4016 effects	Moxifloxacin 400mg n=32 Participants Single 400mg dose of active comparator moxifloxacin (open label) Moxifloxacin 400mg: Active comparator with known effect on QT interval	NST-4016 600mg n=32 Participants Likely therapeutic dose of NST-4016 NST-4016 600mg: Likely maximum therapeutic dose of NST-4016	NST-4016 2000mg n=32 Participants Supratherapeutic dose of NST-4016 NST-4016 2000mg: Supratherapeutic dose of NST-4016
Change From Baseline in QRS Interval (QRS)	-0.2 msec Standard Error 0.17	-0.1 msec Standard Error 0.16	-0.2 msec Standard Error 0.17	0.2 msec Standard Error 0.16

Adverse Events

Placebo Oral Capsule

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Moxifloxacin 400mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

NST-4016 600mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

NST-4016 2000mg

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo Oral Capsule n=32 participants at risk Single dose of placebo to match NST-4016 Placebo oral capsule: Placebo for comparison with moxifloxacin and potential NST-4016 effects	Moxifloxacin 400mg n=32 participants at risk Single 400mg dose of active comparator moxifloxacin (open label) Moxifloxacin 400mg: Active comparator with known effect on QT interval	NST-4016 600mg n=32 participants at risk Likely therapeutic dose of NST-4016 NST-4016 600mg: Likely maximum therapeutic dose of NST-4016	NST-4016 2000mg n=32 participants at risk Supratherapeutic dose of NST-4016 NST-4016 2000mg: Supratherapeutic dose of NST-4016
Nervous system disorders Cerebrovascular accident	0.00% 0/32 • 3.5 months	0.00% 0/32 • 3.5 months	0.00% 0/32 • 3.5 months	3.1% 1/32 • Number of events 1 • 3.5 months

Other adverse events

Measure	Placebo Oral Capsule n=32 participants at risk Single dose of placebo to match NST-4016 Placebo oral capsule: Placebo for comparison with moxifloxacin and potential NST-4016 effects	Moxifloxacin 400mg n=32 participants at risk Single 400mg dose of active comparator moxifloxacin (open label) Moxifloxacin 400mg: Active comparator with known effect on QT interval	NST-4016 600mg n=32 participants at risk Likely therapeutic dose of NST-4016 NST-4016 600mg: Likely maximum therapeutic dose of NST-4016	NST-4016 2000mg n=32 participants at risk Supratherapeutic dose of NST-4016 NST-4016 2000mg: Supratherapeutic dose of NST-4016
Gastrointestinal disorders Gastrointestinal disturbance	12.5% 4/32 • Number of events 4 • 3.5 months	18.8% 6/32 • Number of events 6 • 3.5 months	12.5% 4/32 • Number of events 4 • 3.5 months	46.9% 15/32 • Number of events 15 • 3.5 months

Additional Information

Dr Patrick Round

NorthSea Therapeutics BV

Phone: +44(0)7979502770

Email: patrick.round@northseatherapeutics.com

Results disclosure agreements

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