Safety and Tolerability Study of N6022 in Healthy Subjects

• Sponsor: Nivalis Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01147406
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arms: 2
• Duration (Months): 10
• Patients Per Site Per Month: 4.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of N6022 in healthy subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: N6022; Drug: Placebo	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Dose Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effect of N6022 in Healthy Subjects
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active N6022	Drug: N6022; 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.
Placebo Comparator: Placebo Placebo	Drug: Placebo; This will be 0.9% normal saline given over 1, 3, or 9 minutes IV bolus.; Other Names: N6022

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parexel Early Phase Unit	Baltimore	Maryland	United States	21225

Sponsors and Collaborators

• Nivalis Therapeutics, Inc.

Investigators

• Principal Investigator: Ronald Goldwater, MDCM, MSc(A), Parexel

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nivalis Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01147406
• Other Study ID Numbers: N6022-1H1-01
• First Posted: Jun 22, 2010
• Last Update Posted: Mar 7, 2014
• Last Verified: Jan 1, 2014

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohorts 2 and 4	Cohort 3	Cohort 5	Cohort 6	Placebo
Arm/Group Description	5 mg of N6022 was given intravenously daily for 7 days	15 mg of N6022 was given intravenously daily for 7 days	45 mg of N6022 was to be given intravenously daily for 7 days however, the actual amount was 27.5 mg.	25 mg of N6022 was given intravenously daily for 7 days	35 mg of N6022 was given intravenously daily for 7 days	Not Active - Placebo
Period Title: Overall Study
STARTED	6	12	1	6	6	10
COMPLETED	6	12	1	6	6	10
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2 & 4	Cohort 3	Cohort 5	Cohort 6	Placebo	Total
Arm/Group Description	N6022 - Active 5 mg	N6022 - Active 15 mg	N6022 - Active 45 mg (actual *27.5 mg)	N6022 - Active 25 mg	N6022 - Active 35 mg	Not Active - Placebo	Total of all reporting groups
Overall Participants	6	12	1	6	6	10	41
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	6 100%	12 100%	1 100%	6 100%	6 100%	10 100%	41 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	6 100%	12 100%	1 100%	6 100%	6 100%	10 100%	41 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	5 83.3%	9 75%	1 100%	4 66.7%	5 83.3%	6 60%	30 73.2%
White	1 16.7%	3 25%	0 0%	2 33.3%	1 16.7%	4 40%	11 26.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 10%	2 4.9%
Not Hispanic or Latino	6 100%	12 100%	1 100%	5 83.3%	6 100%	9 90%	39 95.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	12 100%	1 100%	6 100%	6 100%	10 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of a Single Ascending Doses of Intravenous N6022 in Healthy Volunteers
Description	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

Outcome Measure Data

Analysis Population Description

Any subject that received active IMP or placebo

Arm/Group Title	Cohort 1	Cohort 2 and 4	Cohort 3	Cohort 5	Cohort 6	Placebo
Arm/Group Description	N6022 - Active 5 mg	N6022 - Active 15 mg	N6022 - Active 45 mg	N6022 - Active 25 mg	N6022 - Active 35 mg	Not Active - Placebo
Measure Participants	6	12	1	6	6	10
Number [Adverse Events]	1	4	1	0	1	2

2. Secondary Outcome

Title	Maximum N6022 and Metabolite Concentrations in Plasma Within 24 Hours of End of Administration
Description	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

Outcome Measure Data

Analysis Population Description

Any subject that received the active IMP or placebo

Arm/Group Title	Cohort 1	Cohort 2 and 4	Cohort 3	Cohort 5	Cohort 6	Placebo
Arm/Group Description	N6022 - Active 5 mg	N6022 - Active 15 mg	N6022 - Active 45 mg (actual *27.5 mg)	N6022 - Active 25 mg	N6022 - Active 35 mg	Not Active - Placebo
Measure Participants	6	12	1	6	6	10
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	311 (86.6)	1570 (51.5)	1590 (0)	3330 (42.1)	4030 (55.3)	0 (0)

Adverse Events

Time Frame	6 months and 2 weeks
Arm/Group Title	Cohort 1		Cohort 2 and 4		Cohort 3		Cohort 5		Cohort 6		Placebo
Arm/Group Description	N6022 - Active 5 mg		N6022 - Active 15 mg		N6022 - Active 45 mg		N6022 - Active 25 mg		N6022 - Active 35 mg		Not Active - Placebo
All Cause Mortality
	Cohort 1		Cohort 2 and 4		Cohort 3		Cohort 5		Cohort 6		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1		Cohort 2 and 4		Cohort 3		Cohort 5		Cohort 6		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/12 (0%)		0/1 (0%)		0/6 (0%)		0/6 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2 and 4		Cohort 3		Cohort 5		Cohort 6		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		4/12 (33.3%)		1/1 (100%)		0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)
Cardiac disorders
Tachycardia	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Gastrointestinal disorders
Nausea	0/6 (0%)	0	1/12 (8.3%)	1	1/1 (100%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Vomiting	0/6 (0%)	0	0/12 (0%)	0	1/1 (100%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
General disorders
Injection Site Pain	1/6 (16.7%)	1	0/12 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1
Injection Site Hematoma	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Chest Pain	0/6 (0%)	0	0/12 (0%)	0	1/1 (100%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in Extremity	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Nervous system disorders
Dizziness	0/6 (0%)	0	2/12 (16.7%)	2	0/1 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Headache	0/6 (0%)	0	0/12 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1
Sinus Headache	0/6 (0%)	0	0/12 (0%)	0	1/1 (100%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dry Throat	0/6 (0%)	0	0/12 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Rhinorrhea	0/6 (0%)	0	0/12 (0%)	0	0/1 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Vascular disorders
Hypotension	0/6 (0%)	0	1/12 (8.3%)	1	0/1 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigator agrees with the use of results of the clinical study for the purposes of national and international registration, publication, and information for medical and pharmaceutical professionals. If necessary, the competent authorities will be notified of the investigator's name, address, qualifications, and extent of involvement. An investigator shall not publish any data (poster, abstract, paper, etc.) without having consulted with the Sponsor in advance.