A Phase 1 Study of ARN-6039

NCT03237832 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ARN-CLN-0001
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

This Phase 1 study intends to determine the safety and tolerability of ARN-6039 in healthy subjects.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (5)

• Change in clinical tests results over time

  Assess the results of analytical hematology, serology, and urine tests compared to normal results from baseline to 7 days post administration

  Days -1, 1, 2, 3, and 7

• Change in vital signs over time

  Assess subject vital signs compared to normal results from baseline to 7 days post administration

  Days -1, 1, 2, 3, and 7

• Change in physical assessment over time

  Assess results of subject physical examination compared to normal results from baseline to 7 days post administration

  Days -1, 1, 2, 3, and 7

• Change in electrocardiograms (ECGs) over time

  Assess results of subject electrocardiograms compared to normal from baseline to 7 days post administration

  Days -1, 1, 2, 3, and 7

• Determine the incidence of Treatment Adverse Events (AEs) over time

  Assess any adverse events compared to normal from baseline to 7 days post administration

  Days -1, 1, 2, 3, and 7

Secondary Outcomes (6)

• Assay maximum plasma concentration (Cmax) over time

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36 and 48 hours after dosing

• Assay the time to Cmax (tmax) over time

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36 and 48 hours after dosing

• Assay the area under the plasma concentration time curve from zero to the last measurable concentration (AUC0-t) over time

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36 and 48 hours after dosing

• Assay the terminal half-life (t1/2) over time

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36 and 48 hours after dosing

• Assay the area under the plasma concentration time curve from zero to infinity (AUC0-inf) over time

  0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36 and 48 hours after dosing

Other Outcomes (1)

• Identify possible metabolites of ARN-6039.

  7 days +/- 1 day

Study Arms (5)

Cohort 1

PLACEBO COMPARATOR

Cohort 1 (sentinel group): 1 subject received 50 mg ARN-6039 and 1 subject placebo Cohort 1: 7 subjects received 50 mg ARN-6039 and 1 subject placebo

Drug: ARN-6039; Other: Placebo

Cohort 2

PLACEBO COMPARATOR

Cohort 2 (sentinel group): 1 subject received 100 mg ARN-6039 and 1 subject placebo Cohort 2: 7 subjects received 100 mg ARN-6039 and 1 subject placebo

Drug: ARN-6039; Other: Placebo

Cohort 3

PLACEBO COMPARATOR

Cohort 3 (sentinel group): 1 subject received 150 mg ARN-6039 and 1 subject placebo Cohort 3: 7 subjects received 150 mg ARN-6039 and 1 subject placebo

Drug: ARN-6039; Other: Placebo

Cohort 4

PLACEBO COMPARATOR

Cohort 4 (sentinel group): 1 subject received 200 mg ARN-6039 and 1 subject placebo Cohort : 7 subjects received 200 mg ARN-6039 and 1 subject placebo

Drug: ARN-6039; Other: Placebo

Cohort 5

PLACEBO COMPARATOR

Cohort 5 Period 1, fasted (sentinel group): 1 subject received 300 mg ARN-6039 and 1 subject placebo Cohort 5 Period 1, fasted: 7 subjects received 300 mg ARN-6039 and 1 subject placebo Cohort 5 Period 2, fed (sentinel group): 1 subject received 300 mg ARN-6039 and 1 subject placebo Cohort 5 Period 2, fed: 7 subjects received 300 mg ARN-6039 and 1 subject placebo

Drug: ARN-6039; Other: Placebo

Interventions

ARN-6039 DRUG

Ascending doses per Cohort

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Placebo OTHER

Placebo to match ARN-6039

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Only volunteers who met all of the following criteria were included as study subjects:
• Male or female between 18 and 50 years of age, inclusive.
• Female subjects were not pregnant or lactating.
• Female subjects were postmenopausal (at least 2 years prior to dosing) or surgically sterile. Subjects who claimed postmenopausal status had their status confirmed with a follicle-stimulating hormone (FSH) test. Surgically sterile was defined as: Bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months prior to dosing; or Permanent sterilization (e.g., ESSURE procedure) at least 3 months prior to dosing.
• Subjects had a body mass index (BMI) between 19 and 30 kg/m2 (inclusive) and weighed a minimum of 50 kg (110 lbs).
• Subjects voluntarily consented to participate in this study and provided their written informed consent prior to start of any study-specific procedures.
• Subject was willing and able to comply with all trial requirements.
• Subject was willing and able to remain in the study unit for the entire duration of the confinement period and return for an outpatient visit 7 days after study treatment administration.
• Subject's vital signs (measured sitting after 5 minutes rest) at screening were within the following ranges: heart rate: 40-100 beats per minute \[bpm\]; systolic blood pressure (BP): 90-145 mmHg; diastolic BP: 50-95 mmHg. Out-of-range vital signs could be repeated once. Predose vital signs were assessed by the Principal Investigator or designee (e.g., a medically qualified Sub-Investigator) prior to study drug administration. The Principal Investigator or designee verified the eligibility of each subject with out-of-range vital signs and documented approval prior to dosing.
• Subjects had results within normal range on the following hematology tests performed at screening: hemoglobin, hematocrit, total and differential leukocyte count, and platelet count.
• Subject had results that did not exceed the upper limit of normal range on the following liver function tests performed at screening: aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin.
• If enrolled in Cohort 5 (the food-effect cohort), subject was willing and able to consume the entire high-calorie, high-fat breakfast meal in the designated timeframe required during the fed period.

You may not qualify if:

• Volunteers who presented any of the following criteria were excluded as study subjects:
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal (including cholecystectomy), endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would likely have interfered with the absorption, disposition, metabolism, or excretion of the investigational product, or would have jeopardized the safety of the subject or the validity of the study results.
• History of cancer with the exception of basal cell carcinoma or squamous cell (skin) carcinoma.
• History of seizure (including febrile seizure) or loss of consciousness.
• History of drug or alcohol abuse or dependence (based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria) within the past 2 years.
• Donated blood or plasma or experienced significant loss of blood within 8 weeks prior to admission to the clinic, or planned to donate blood within 1 month after study participation.
• Had a clinically significant abnormal finding on the physical exam, medical history, ECG, or clinical laboratory results at screening.
• Had smoked or used tobacco or nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, etc.) within 30 days prior to the first dose of study medication.
• History or presence of allergic or adverse response to ARN-6039 or related drugs or its excipients.
• Had been on a significantly abnormal diet during the 4 weeks preceding the first dose of study medication.
• Had participated in another clinical trial (randomized subjects only) within 30 days (or 5 half-lives of the investigational product) prior to the first dose of study medication.
• Had used any over-the-counter (OTC) medication, nutritional or dietary supplements, or herbal preparations, (other than acetaminophen and/or multivitamins \[acetaminophen 2 grams/day and multivitamins were allowed up to 48 hours prior to dosing\]), within 7 days prior to the first dose of medication.
• Had used any prescription medication, except hormonal replacement therapy, within 14 days prior to the first dose of study medication.
• Consumed the following beverages or products within the specified time frame prior to admission to the clinic: Alcohol, grapefruit, Seville oranges (marmalade), xanthine, or quinine within 72 hours; or Caffeine or poppy seeds within 48 hours.
• Had been treated with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) enzymes such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication and that in the Investigator's judgment may have impacted subject safety or the validity of the study results.

Sponsors & Collaborators

• Arrien Pharmaceuticals: lead
• Worldwide Clinical Trials: collaborator

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The pharmacist preparing the doses was unblended and was responsible for all drug accountability issues, including preparing, labeling, and dispensing study drug according to the randomization code provided. The unblinded pharmacists were responsible for maintaining the blind, consistent with protocol design, throughout the study. All documentation was filed in the Pharmacy Manual, and access to this manual was restricted to the unblinded pharmacists. The subjects, Principal Investigator, and all other personnel involved with subject assessments were blinded to the actual treatment assignments of the subjects (ARN-6039 or placebo) during the study.
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Determine safety and tolerability of ARN-6039 ascending doses compared to placebo

Study Record Dates

• First Submitted: July 21, 2017
• First Posted: August 3, 2017
• Study Start: May 16, 2016
• Primary Completion: October 6, 2016
• Study Completion: February 1, 2017
• Last Updated: August 3, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Clinical study report currently available.
• Access Criteria: Please contact Dr. Hari Vankayalapati at Arrien Pharmaceuticals LLC (e-mail: hari@arrienpharma.com).