Healthy
Conditions
Brief summary
The purpose of this study is to evaluate the safety and tolerability of N6022 in healthy subjects.
Detailed description
This is a single dose escalation, first-time-in-human study with three ascending cohorts. Eligible subjects will receive a single dose of investigational medicinal product or placebo on Day 1 and will be followed for safety, PK, and PD for 72 hours post dose. Follow-up visits on Day 4 and Day 7 for the end-of-study safety. Participation of an individual subject may last up to 36 days from the time of screening until the end-of-study follow-up visit. Each cohort will enroll a sentinel pair (1:1 randomized to active: placebo). These subjects will be followed for 48 hours postdose and safety data reviewed before the remaining subjects in the cohort receive IMP. A Safety Monitoring Committee will review the seven-day safety data in each cohort before proceeding to the next ascending dose cohort, according to the stopping rules outlined in the protocol.
Interventions
DRUGN6022
This is an injectible formulation which will be given at 5, 15 & 45 mg over 1, 3 and 9 minutes respectively, in single ascending doses.
DRUGPlacebo
This will be 0.9% normal saline given over 1, 3, or 9 minutes IV bolus.
Sponsors
Nivalis Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion: * Subject is healthy Exclusion: * Subject is a current alcohol abuser and/or has a history of illicit drug abuse within six months of entry. * Subject has donated blood (\> 500 mL) or blood products within 56 days prior to Day -1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers | 7 Days | Safety variables - number of adverse events reported during study, changes in vital signs, physical examination findings, telemetry alerts, 12-lead ECG changes, infusion site reactions, O2 saturation changes, and clinical laboratory assessment changes between subjects receiving N6022 versus placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum N6022 and Metabolite Concentrations in Plasma Within 24 Hours of End of Administration | 24 hours | Concentrations of N6022 and metabolite \[N61149)\], collected on Days 1 and 7; predose, end of infusion, and at 10 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 16, and 24 hours post-dose (the 24 hour postdose collected prior to the start of infusion on Day 2). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 N6022 - Active 5 mg | 6 |
| Cohort 2 & 4 N6022 - Active 15 mg | 12 |
| Cohort 3 N6022 - Active 45 mg (actual \*27.5 mg) | 1 |
| Cohort 5 N6022 - Active 25 mg | 6 |
| Cohort 6 N6022 - Active 35 mg | 6 |
| Placebo Not Active - Placebo | 10 |
| Total | 41 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 & 4 | Cohort 3 | Cohort 5 | Cohort 6 | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 12 Participants | 1 Participants | 6 Participants | 6 Participants | 10 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 12 Participants | 1 Participants | 5 Participants | 6 Participants | 9 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 1 Participants | 4 Participants | 5 Participants | 6 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 11 Participants |
| Region of Enrollment United States | 6 participants | 12 participants | 1 participants | 6 participants | 6 participants | 10 participants | 41 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 12 Participants | 1 Participants | 6 Participants | 6 Participants | 10 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 4 / 12 | 1 / 1 | 0 / 6 | 1 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 12 | 0 / 1 | 0 / 6 | 0 / 6 | 0 / 10 |
Outcome results
Primary
Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers
Safety variables - number of adverse events reported during study, changes in vital signs, physical examination findings, telemetry alerts, 12-lead ECG changes, infusion site reactions, O2 saturation changes, and clinical laboratory assessment changes between subjects receiving N6022 versus placebo.
Time frame: 7 Days
Population: Any subject that received active IMP or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers | 1 Adverse Events |
| Cohort 2 and 4 | Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers | 4 Adverse Events |
| Cohort 3 | Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers | 1 Adverse Events |
| Cohort 5 | Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers | 0 Adverse Events |
| Cohort 6 | Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers | 1 Adverse Events |
| Placebo | Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers | 2 Adverse Events |
Secondary
Maximum N6022 and Metabolite Concentrations in Plasma Within 24 Hours of End of Administration
Concentrations of N6022 and metabolite \[N61149)\], collected on Days 1 and 7; predose, end of infusion, and at 10 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 16, and 24 hours post-dose (the 24 hour postdose collected prior to the start of infusion on Day 2).
Time frame: 24 hours
Population: Any subject that received the active IMP or placebo
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Maximum N6022 and Metabolite Concentrations in Plasma Within 24 Hours of End of Administration | 311 ng/mL | Geometric Coefficient of Variation 86.6 |
| Cohort 2 and 4 | Maximum N6022 and Metabolite Concentrations in Plasma Within 24 Hours of End of Administration | 1570 ng/mL | Geometric Coefficient of Variation 51.5 |
| Cohort 3 | Maximum N6022 and Metabolite Concentrations in Plasma Within 24 Hours of End of Administration | 1590 ng/mL | Geometric Coefficient of Variation 0 |
| Cohort 5 | Maximum N6022 and Metabolite Concentrations in Plasma Within 24 Hours of End of Administration | 3330 ng/mL | Geometric Coefficient of Variation 42.1 |
| Cohort 6 | Maximum N6022 and Metabolite Concentrations in Plasma Within 24 Hours of End of Administration | 4030 ng/mL | Geometric Coefficient of Variation 55.3 |
| Placebo | Maximum N6022 and Metabolite Concentrations in Plasma Within 24 Hours of End of Administration | 0 ng/mL | Geometric Coefficient of Variation 0 |