Clinical trial NCT02478333: A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of ALS-008176 in Healthy Japanese Adult Participants
Official title: A Double-Blind, Placebo-Controlled, Randomized, Single Ascending Dose Study to Investigate Safety, Tolerability, and Pharmacokinetics of ALS-008176 in Healthy Japanese Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Respiratory Syncytial Virus Infections
Keywords: Healthy
ALS-008176
Japanese adult participants
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2015-06-23
Enrollment: 24
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ALS-008176 following oral administration of single ascending dose of ALS-008176 in healthy Japanese adult participants.

Detailed description: This is a double-blind (test or experiment in which neither the person giving the treatment nor the patient knows which treatment the patient is receiving), placebo-controlled, randomized (study medication assigned to participants by chance) and single-center study of ALS-008176. The duration of study will be approximately 6 weeks for each participant. The study consists of 3 parts: Screening Phase (28 days before study commences on Day 1); double-blind Treatment Phase (single oral dose of ALS-008176 or placebo on Day 1 under fasted condition); and Follow up Phase (up to 14 days after study drug administration). All the eligible participants will be randomly assigned to receive either a single oral dose of ALS-008176 or placebo in each group. The planned doses will be escalated in a stepwise fashion if the safety and tolerability in the preceding dose is found acceptable. Participants in Group 1 will receive ALS-008176, 250 milligram (mg) or placebo, Group 2 will receive ALS-008176, 500 mg or placebo and Group 3 will receive ALS-008176, 750 mg or placebo. Study drug will be administered following a 10-hour overnight fast. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Pharmacokinetics of ALS-008176, ALS-008206, ALS-008112, and its metabolite ALS 008144 will be evaluated primarily. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Be a Japanese participant whose parents and grandparents are Japanese as determined by the participant's verbal report
* Each participant must sign an Informed Consent Form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study
* Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
* A female participant must be either:

  1. Not of childbearing potential: postmenopausal \[greater than (\>) 45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level \>40 International Units (IU)/ liter (L) (to be confirmed at Screening for all postmonopausal women)\] OR
  2. Permanently sterilized (eg, bilateral tubal occlusion \[which includes tubal ligation procedures as consistent with local regulations\], hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or otherwise incapable of becoming pregnant, OR c. If of childbearing potential and heterosexually active, practicing an effective method of birth control before entry and agree to continue to use two effective methods of contraception throughout the study and for at least 30 days after receiving the study drug
* Participant must be a non-smoker for at least one month prior to screening

Exclusion Criteria:

* Participant has a history of current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the Investigator considers should exclude the participant or that could interfere with the interpretation of the study results
* Participant with a past history of heart arrhythmias (extrasystoli, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome (eg, hypokalemia, family history of long QT Syndrome)
* Participant has creatinine clearance of lower than 70 millilitre (mL)/min
* Participant has taken any disallowed therapies as noted in protocol, Pre-study and Concomitant Therapy before the planned study drug
* Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Time of Last Measurable Plasma Concentration (Tlast) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration (AUC [0-last]) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From 0 to Infinite Time (AUC[0-infinity]) Post Dose of ALS 008176, ALS-008206, ALS-008112, and ALS-008144
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Percentage of Area Under the Plasma Concentration-Time Curve Obtained by Extrapolation (%AUC[infinity,ex])
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Apparent Initial Elimination Rate Constant (Lambda [alpha]) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Apparent Terminal Elimination Rate Constant (Lambda [z]) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Apparent Initial Half-life (t[1/2alpha]) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Apparent Terminal Half-life (t[1/2term]) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144
timeFrame: Pre-dose; 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
measure: Amount of ALS 008176, ALS-008206, ALS-008112, and ALS-008144 excreted in Urine (Ae[x-y])
timeFrame: Up to 48 hours post-dose
measure: Total Amount of ALS 008176, ALS-008206, ALS-008112, and ALS-008144 excreted in Urine (Ae[total])
timeFrame: Up to 48 hours post-dose
measure: Total Percentage of ALS 008176, ALS-008206, ALS-008112, and ALS-008144 dose excreted into urine
timeFrame: Up to 48 hours post-dose
measure: Renal clearance
timeFrame: Up to 48 hours post-dose
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs) and Serious AEs
timeFrame: Screening up to follow-up (14 days after dose administration)
Other outcomes:
Locations:
city: Fukuoka
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References: