A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of ALS-008176 in Healthy Japanese Adult Participants

NCT02478333 | Completed Phase 1

• 2 other identifiers: CR10718064041575RSV1001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Respiratory Syncytial Virus Infections

Keywords

Healthy; ALS-008176; Japanese adult participants

Outcome Measures

Primary Outcomes (14)

• Maximum Plasma Concentration (Cmax) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144

  The Cmax is the maximum observed plasma concentration of ALS 008176, ALS-008206, ALS-008112, and ALS-008144.

  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

• Time to Reach the Maximum Plasma Concentration (Tmax) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144

  The Tmax is the time to reach the maximum observed plasma concentration of ALS 008176, ALS-008206, ALS-008112, and ALS-008144.

  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

• Time of Last Measurable Plasma Concentration (Tlast) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144

  Time of last measurable (non-below quantification limit \[non-BQL\]) plasma concentration.

  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

• 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

  The AUC (0-last) is the area under the plasma ALS 008176, ALS-008206, ALS-008112, and ALS-008144 concentration-time curve from time 0 to time of the last observed (non-BQL) quantifiable concentration, calculated by linear-linear trapezoidal summation.

  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

• 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

  The AUC (0-infinity) is the area under the plasma concentration-time curve from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), in which AUC(0-last) is area under the plasma ALS 008176, ALS-008206, ALS-008112, and ALS-008144 concentration-time curve from time zero to time of the last quantifiable concentration, C(last) is the last observed (non-BQL) quantifiable concentration and lambda(z) is elimination rate constant. Extrapolations of more than 20.00% of the total AUC are reported as approximations.

  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

• Percentage of Area Under the Plasma Concentration-Time Curve Obtained by Extrapolation (%AUC[infinity,ex])

  The %AUC\[infinity,ex\] is calculated by dividing the difference of AUC(0-infinity) and AUC(0-last) by AUC(0-infinity) and then multiplying by 100, (AUC\[0-infinity\] - AUC\[0-last\])\*100/AUC\[0-infinity\].

  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

• Apparent Initial Elimination Rate Constant (Lambda [alpha]) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144

  The Lambda (alpha) determined by linear regression of the first elimination phase of the ln-linear plasma concentration-time curve.

  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

• Apparent Terminal Elimination Rate Constant (Lambda [z]) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144

  The Lambda (z) determined by linear regression of the terminal points of the ln-linear plasma concentration-time curve.

  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

• Apparent Initial Half-life (t[1/2alpha]) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144

  The t(1/2alpha) is defined as 0.693/Lambda (alpha).

  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

• Apparent Terminal Half-life (t[1/2term]) of ALS 008176, ALS-008206, ALS-008112, and ALS-008144

  The t(1/2term) is defined as 0.693/Lambda (z).

  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

• Amount of ALS 008176, ALS-008206, ALS-008112, and ALS-008144 excreted in Urine (Ae[x-y])

  Amount excreted into urine over a given time interval, calculated from the urinary drug concentration of the collection interval x to y hours post dosing multiplied with the associated urine volume of the interval.

  Up to 48 hours post-dose

• Total Amount of ALS 008176, ALS-008206, ALS-008112, and ALS-008144 excreted in Urine (Ae[total])

  Total amount excreted into urine, calculated by adding the amounts of the individual intervals together {Ae\[0-48hours(h)\]}.

  Up to 48 hours post-dose

• Total Percentage of ALS 008176, ALS-008206, ALS-008112, and ALS-008144 dose excreted into urine

  Total percentage of the dose excreted into urine, calculated as 100 \* (Ae\[total\]/Dose).

  Up to 48 hours post-dose

• Renal clearance

  Renal clearance calculated as Ae (0-48h)/AUC (0-48h).

  Up to 48 hours post-dose

Secondary Outcomes (1)

• Number of Participants with Adverse Events (AEs) and Serious AEs

  Screening up to follow-up (14 days after dose administration)

Study Arms (3)

ALS-008176 (250 mg) or Placebo

EXPERIMENTAL

Participants will receive ALS-008176, 250 milligram (mg) or placebo oral suspension once on Day 1 under fasted conditions.

Drug: ALS-008176 (250 mg); Other: Placebo

ALS-008176 (500 mg) or Placebo

EXPERIMENTAL

Participants will receive ALS-008176, 500 milligram (mg) or placebo oral suspension once on Day 1 under fasted conditions.

Drug: ALS-008176 (500 mg); Other: Placebo

ALS-008176 (750 mg) or Placebo

EXPERIMENTAL

Participants will receive ALS-008176, 750 milligram (mg) or placebo oral suspension once on Day 1 under fasted conditions.

Drug: ALS-008176 (750 mg); Other: Placebo

Interventions

ALS-008176 (250 mg) DRUG

Participants will receive ALS-008176, 250 mg oral suspension once on Day 1 under fasted conditions.

ALS-008176 (250 mg) or Placebo

ALS-008176 (500 mg) DRUG

Participants will receive ALS-008176, 500 mg oral suspension once on Day 1 under fasted conditions.

ALS-008176 (500 mg) or Placebo

ALS-008176 (750 mg) DRUG

Participants will receive ALS-008176, 750 mg oral suspension once on Day 1 under fasted conditions.

ALS-008176 (750 mg) or Placebo

Placebo OTHER

Participants will receive placebo oral suspension once on Day 1 under fasted conditions.

ALS-008176 (250 mg) or Placebo; ALS-008176 (500 mg) or Placebo; ALS-008176 (750 mg) or Placebo

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (1)

Unknown Facility

Fukuoka, Japan

Location

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

4'-chloromethyl-2'-deoxy-3',5'-di-O-isobutyryl-2'-fluorocytidine

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• Janssen Pharmaceutical K.K., Japan Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2015
• First Posted: June 23, 2015
• Study Start: May 1, 2015
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 11, 2016

Record last verified: 2016-07

Locations

JP (1)