A Drug-Drug Interaction Study to Evaluate the Effect of AL-794 on the Pharmacokinetics of Oseltamivir and JNJ-63623872

NCT02888327 | Completed Phase 1

• 1 other identifier: AL-794-802
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, four group, fixed-sequence study will evaluate the safety and pharmacokinetic interaction of AL-794 on oseltamivir, JNJ-63623872 (formerly VX-787) and probes for P-glycoprotein, CYP3A and OATP1B1 in healthy volunteers.

Conditions

Influenza in Humans

Outcome Measures

Primary Outcomes (4)

• Maximum observed plasma concentration (Cmax) for ALS-033719, ALS-033927, oseltamivir, oseltamivir carboxylate, JNJ-63623872, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin

  At 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose on days 7, 8, and 14 for ALS-033719, ALS-033927, and JNJ-63623872

• Area under plasma concentration-time curve from time 0 to dosing interval (tau) (AUC0-τ) for ALS-033719 and ALS-033927, oseltamivir, oseltamivir carboxylate, and JNJ-63623872

  At 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose on days 7, 8, and 14 for ALS-033719, ALS-033927, and JNJ-63623872

• Area under plasma concentration-time curve from time 0 to last measurable plasma concentration (AUClast) for digoxin, midazolam 1'-OH-midazolam, and pitavastatin

  At 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose on Days 1, 11, and 17 for oseltamivir, oseltamivir carboxylate, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin

• Maximum observed plasma concentration (Cmax) for oseltamivir, oseltamivir carboxylate, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin

  At 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose on Days 1, 11, and 17 for oseltamivir, oseltamivir carboxylate, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin

Secondary Outcomes (9)

• Last observed plasma concentration (Clast) for ALS-033719, ALS-033927, oseltamivir, oseltamivir carboxylate, JNJ-63623872, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin when applicable

  At 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose on days 7, 8, and 14 for ALS-033719, ALS-033927, and JNJ-63623872, Days 1, 11, and 17 for oseltamivir, oseltamivir carboxylate, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin

• Terminal elimination half-life (t½) for ALS-033719, ALS-033927, oseltamivir, oseltamivir carboxylate, JNJ-63623872, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin when applicable

  At 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose on days 7, 8, and 14 for ALS-033719, ALS-033927, and JNJ-63623872, Days 1, 11, and 17 for oseltamivir, oseltamivir carboxylate, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin

• Time of the maximum observed plasma concentration (tmax) for ALS-033719, ALS-033927, oseltamivir, oseltamivir carboxylate, JNJ-63623872, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin when applicable

  At 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose on days 7, 8, and 14 for ALS-033719, ALS-033927, and JNJ-63623872, Days 1, 11, and 17 for oseltamivir, oseltamivir carboxylate, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin

• Time to last measurable plasma concentration (tlast) for ALS-033719, ALS-033927, oseltamivir, oseltamivir carboxylate, JNJ-63623872, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin when applicable

  At 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose on days 7, 8, and 14 for ALS-033719, ALS-033927, and JNJ-63623872, Days 1, 11, and 17 for oseltamivir, oseltamivir carboxylate, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin

• Apparent oral clearance (CL/F) for ALS-033719, ALS-033927, oseltamivir, oseltamivir carboxylate, JNJ-63623872, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin when applicable

  At 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post dose on days 7, 8, and 14 for ALS-033719, ALS-033927, and JNJ-63623872, Days 1, 11, and 17 for oseltamivir, oseltamivir carboxylate, digoxin, midazolam, 1'-OHmidazolam, and pitavastatin

Study Arms (4)

Oseltamivir and AL-794

OTHER

Oseltamivir alone and with AL-794 over fourteen days.

Drug: AL-794; Drug: Oseltamivir

Digoxin, Midazolam, and AL-794

OTHER

Single doses of Digoxin and Midazolam with and without AL-794 over seventeen days.

Drug: AL-794; Drug: Digoxin; Drug: Midazolam

Pitavastatin and AL-794

OTHER

Single doses of Pitavastatin with and without AL-794 over seventeen days.

Drug: AL-794; Drug: Pitavastatin

JNJ-63623872 and AL-794

OTHER

JNJ-63623872 alone and with AL-794 over fourteen days.

Drug: AL-794; Drug: JNJ-63623872

Interventions

AL-794 DRUG

Digoxin, Midazolam, and AL-794; JNJ-63623872 and AL-794; Oseltamivir and AL-794; Pitavastatin and AL-794

Oseltamivir DRUG

Oseltamivir and AL-794

Digoxin DRUG

Digoxin, Midazolam, and AL-794

Midazolam DRUG

Digoxin, Midazolam, and AL-794

Pitavastatin DRUG

Pitavastatin and AL-794

JNJ-63623872 DRUG

JNJ-63623872 and AL-794

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject has provided written consent.
• In the investigator's opinion, the subject is able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions and is likely to complete the study as planned.
• Subject is in good health as deemed by the investigator, based on the findings of a medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG).
• Male or female, 18-60 years of age.
• Body mass index (BMI) 18-30 kg/m2, inclusive. The minimum weight is 50 kg.
• A female subject is eligible to participate in this study if she is of non-childbearing potential (defined as females with a documented tubal ligation, bilateral oophorectomy or hysterectomy) or postmenopausal (defined as 12 months of spontaneous amenorrhea and follicle stimulating hormone level within the laboratory's reference range for postmenopausal females). A postmenopausal female receiving hormone replacement therapy who is willing to discontinue hormone therapy 28 days before study drug dosing and agrees to remain off hormone replacement therapy for the duration of the study may be eligible for study participation. Females must refrain from donating eggs (ova, oocytes) for the purposes of assisted reproduction from check-in through 6 months after dosing.
• If male, subject is surgically sterile or practicing acceptable forms of birth control until 90 days after the end of the study. Males must agree to refrain from sperm donation from check-in through 90 days after dosing.

You may not qualify if:

• Men whose female partners are pregnant or contemplating pregnancy from the date of screening until 90 days after their last dose of study drugs.
• Clinically significant laboratory abnormalities or abnormalities which are deemed to interfere with the ability to interpret study data.
• Creatinine clearance of less than 60 mL/min (MDRD).
• Total bilirubin, ALT, AST, or alkaline phosphatase \>1.2× upper limit of normal (documented Gilbert's permitted).
• Clinically significant cardiovascular, respiratory, renal, gastrointestinal, hematologic, neurologic, thyroid or any other medical illness or psychiatric disorder, as determined by the Investigator and/or Sponsor's Medical Monitor.
• Positive screening test for influenza, hepatitis A, B, C or human immunodeficiency virus (HIV) serology.
• Any condition that, in the opinion of the investigator, would compromise the study's objectives or the well-being of the subject or prevent the subject from meeting the study requirements.
• Participation in an investigational drug trial or having received an investigational vaccine within 3 months or 5 half-lives (whichever is longer) prior to study medication.
• Clinically significant abnormal ECG findings. Particularly, a history or family history of prolonged QT syndrome (eg, torsade de pointes), pre-existing sinus node disease, (incomplete) AV block, heart failure, or sudden cardiac death; or a corrected QT interval (QTcF or QTcB) \>450 milliseconds for male subjects and \>470 milliseconds for female subjects at the screening visit.
• Clinically significant blood loss or elective blood donation of significant volume (ie, \>500 mL) within 90 days of first dose of study drug; \>1 unit of plasma within 7 days of first dose of study drug.
• Clinically significant abnormal heart rate, respiratory rate, temperature or blood pressure values outside of the normal range, per local standards (evaluated in a semi-recumbent or recumbent position after 5 minutes of rest) which are considered clinically significant. One repeat measurement after an additional 5 minutes of rest is permitted in one visit day.
• Evidence or current diagnosis of sleep apnea.
• Evidence of clinically significant infection within 2 weeks prior to admission.
• Unwilling to abstain from alcohol for at least 1 week prior to the start of dosing through the Study Completion visit.
• History of regular alcohol intake \>14 units per week of alcohol for females and \>21 units per week for males (one unit is defined as 8 g alcohol) within 3 months of the screening visit.

Sponsors & Collaborators

• Alios Biopharma Inc.: lead

Study Sites (1)

Hammersmith Medicines Research

London, United Kingdom

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

sfericase; Oseltamivir; Digoxin; Midazolam; pitavastatin; pimodivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Adeep Puri

  Hammersmith Medicines Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: September 5, 2016
• Study Start: July 31, 2016
• Primary Completion: May 30, 2017
• Study Completion: May 30, 2017
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

GB (1)