Dyslipidemias
Conditions
Brief summary
This is a Phase 1, single centre, randomised, double blind (except for moxifloxacin), placebo and positive controlled, 4 way crossover study assessing the ECG effects of therapeutic and supratherapeutic doses of icosabutate in healthy male and female subjects.
Interventions
DRUGNST-4016 600mg
Likely maximum therapeutic dose of NST-4016
DRUGPlacebo oral capsule
Placebo for comparison with moxifloxacin and potential NST-4016 effects
Active comparator with known effect on QT interval
DRUGNST-4016 2000mg
Supratherapeutic dose of NST-4016
Sponsors
NorthSea Therapeutics B.V.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* 1\. Males or females, of any race, between 18 and 55 years of age, inclusive, at Screening. * 2\. Body mass index (BMI) between 18.0 and 33.0 kg/m2, inclusive, at Screening * 3\. In good health
Exclusion criteria
* 1\. An uninterpretable or abnormal ECG at Screening and/or Check in * 2\. History of risk factors for Torsades de Pointes * 3\. sustained supine systolic blood pressure \>140 mmHg or \<90 mmHg * 4\. Unstable cardiovascular disease, including recent myocardial infarction or cardiac arrhythmia. * 5\. Female subjects who are pregnant (or planning to become pregnant within 90 days after the final dose administration) or are currently lactating * 6\. Subjects who, in the opinion of the Investigator (or designee), should not participate in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | 24 hours | Electrocardiogram measurement of the maximum absolute change from baseline in Fridericia's correction for QT interval (QTcF) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Heart Rate (HR) | 24 hours | Electrocardiogram measurement of change from baseline in heart rate (HR) maximum values presented |
| Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | 24 hours | Electrocardiogram measurement of change from baseline in Fridericia's correction for QT interval (QTcF) |
| Change From Baseline in PR Interval (PR) | 24 hours | Electrocardiogram measurement of change from baseline in PR interval (PR) |
| Change From Baseline in QRS Interval (QRS) | 2 hours | Electrocardiogram measurement of change from baseline in QRS interval (QRS) |
Countries
United Kingdom
Participant flow
Pre-assignment details
This was a cross over study so 32 subjects each completed 4 treatment arms
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants were randomized to receive all 4 interventions | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment United Kingdom | 32 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 4 / 32 | 6 / 32 | 4 / 32 | 15 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 | 0 / 32 | 1 / 32 |
Outcome results
Primary
Change From Baseline in Fridericia's Correction for QT Interval (QTcF)
Electrocardiogram measurement of the maximum absolute change from baseline in Fridericia's correction for QT interval (QTcF)
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Oral Capsule | Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | -4.6 msec | Standard Error 1.52 |
| Moxifloxacin 400mg | Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | 11.5 msec | Standard Error 0.88 |
| NST-4016 600mg | Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | -6.0 msec | Standard Error 1.39 |
| NST-4016 2000mg | Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | -6.1 msec | Standard Error 1.42 |
Comparison: The primary analysis was based on concentration-QTc modeling of the relationship between icosabutate and delta delta QTcF, with the intent to exclude an effect \> 10 msec at clinically relevant icosabutate plasma concentrations.~Assay sensitivity was evaluated by concentration-QTc analysis of the effect on delta delta QTcF of moxifloxacin using a similar model as for the primary analysis.
Secondary
Change From Baseline in Fridericia's Correction for QT Interval (QTcF)
Electrocardiogram measurement of change from baseline in Fridericia's correction for QT interval (QTcF)
Time frame: 24 hours
Population: The largest change in QTcF for each arm during the study is presented below
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Oral Capsule | Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | -4.6 msec | Standard Error 1.52 |
| Moxifloxacin 400mg | Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | 11.5 msec | Standard Error 0.88 |
| NST-4016 600mg | Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | -6.0 msec | Standard Error 1.39 |
| NST-4016 2000mg | Change From Baseline in Fridericia's Correction for QT Interval (QTcF) | -5.7 msec | Standard Error 1.39 |
Secondary
Change From Baseline in Heart Rate (HR)
Electrocardiogram measurement of change from baseline in heart rate (HR) maximum values presented
Time frame: 24 hours
Population: maximum values of change in heart rate from baseline over the 24 hours post dose
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Oral Capsule | Change From Baseline in Heart Rate (HR) | 9.9 beats per minute | Standard Error 0.86 |
| Moxifloxacin 400mg | Change From Baseline in Heart Rate (HR) | 12.2 beats per minute | Standard Error 0.85 |
| NST-4016 600mg | Change From Baseline in Heart Rate (HR) | 12.6 beats per minute | Standard Error 0.88 |
| NST-4016 2000mg | Change From Baseline in Heart Rate (HR) | 15.6 beats per minute | Standard Error 0.85 |
Secondary
Change From Baseline in PR Interval (PR)
Electrocardiogram measurement of change from baseline in PR interval (PR)
Time frame: 24 hours
Population: maximum change from baseline during the study period is reported
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Oral Capsule | Change From Baseline in PR Interval (PR) | -11.0 msec | Standard Error 1.32 |
| Moxifloxacin 400mg | Change From Baseline in PR Interval (PR) | -11.9 msec | Standard Error 1.3 |
| NST-4016 600mg | Change From Baseline in PR Interval (PR) | -11.4 msec | Standard Error 1.36 |
| NST-4016 2000mg | Change From Baseline in PR Interval (PR) | -12.4 msec | Standard Error 1.3 |
Secondary
Change From Baseline in QRS Interval (QRS)
Electrocardiogram measurement of change from baseline in QRS interval (QRS)
Time frame: 2 hours
Population: The data presented is from the 2 hour time point corresponding to T max
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Oral Capsule | Change From Baseline in QRS Interval (QRS) | -0.2 msec | Standard Error 0.17 |
| Moxifloxacin 400mg | Change From Baseline in QRS Interval (QRS) | -0.1 msec | Standard Error 0.16 |
| NST-4016 600mg | Change From Baseline in QRS Interval (QRS) | -0.2 msec | Standard Error 0.17 |
| NST-4016 2000mg | Change From Baseline in QRS Interval (QRS) | 0.2 msec | Standard Error 0.16 |