A Phase 1 Study of ARN-6039

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT03237832
• Date of registration: 21/07/2017
• Prospective Registration: No
• Primary sponsor: Arrien Pharmaceuticals
• Public title: A Phase 1 Study of ARN-6039 ARN-6039
• Scientific title: A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability, and Pharmacokinetic Study of Single Ascending Oral Doses of ARN-6039 in Healthy Adult Subjects.
• Date of first enrolment: May 16, 2016
• Target sample size: 60
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03237832
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Health Services Research. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Key inclusion & exclusion criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

- Had a positive urine screen for drugs of abuse (amphetamines, barbiturates,
benzodiazepines, cocaine, cannabinoids, opiates) or cotinine.

- Had a positive test for hepatitis B surface antigen, hepatitis C antibody, or human
immunodeficiency virus (HIV) at screening or had been previously treated for hepatitis
B, hepatitis C, or HIV infection.

- Was, for any reason, deemed by the investigator to be inappropriate for this study,
including subjects who were unable to communicate or cooperate with the investigator
or designee.

- Female with a positive pregnancy test result.



Age minimum: 18 Years
Age maximum: 50 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Drug: ARN-6039

Other: Placebo

Primary Outcome(s)

Change in clinical tests results over time [Time Frame: Days -1, 1, 2, 3, and 7]

Change in electrocardiograms (ECGs) over time [Time Frame: Days -1, 1, 2, 3, and 7]

Determine the incidence of Treatment Adverse Events (AEs) over time [Time Frame: Days -1, 1, 2, 3, and 7]

Change in physical assessment over time [Time Frame: Days -1, 1, 2, 3, and 7]

Change in vital signs over time [Time Frame: Days -1, 1, 2, 3, and 7]

Secondary Outcome(s)

Assay the area under the plasma concentration time curve from zero to infinity (AUC0-inf) over time [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 [Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36 and 48 hours after dosing]

Assay maximum plasma concentration (Cmax) over time [Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36 and 48 hours after dosing]

Assay the apparent oral clearance (CL/F) over time [Time Frame: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36 and 48 hours after dosing]

Secondary ID(s)

ARN-CLN-0001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Worldwide Clinical Trials