Clinical trial NCT02512562: A Study to Evaluate the Effect of ACH-3102 and Simeprevir on AL-335 Pharmacokinetics in Healthy Volunteers
Official title: A Phase-1, Open-label, Two Group, Fixed-Sequence Study to Evaluate the Effect of ACH-3102 and Simeprevir on AL-335 Pharmacokinetics in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Hepatitis C
Lead sponsor: Alios Biopharma Inc.
Sponsor class: INDUSTRY
Collaborators: name: Alexion Pharmaceuticals, Inc.
First posted: 2015-07-31
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, two-group, fixed-sequence study to evaluate the effect of ACH-3102 and Simeprevir on AL-335 pharmacokinetics in healthy volunteers.


Eligibility criteria: Inclusion Criteria:

1. Subject has provided written consent.
2. 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.
3. 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 ECG.
4. Male or female, 18-60 years of age.
5. Body mass index (BMI) 18-32 kg/m2, inclusive. The minimum weight is 50 kg. No more than 25% of subjects may be enrolled with a BMI ≥ 30 kg/m2.
6. 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 (FSH) level within the laboratory's reference range for postmenopausal females)). A post-menopausal 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.
7. If male, subject is surgically sterile or practicing specific forms of birth control until 6 months after the end of the study. Males must agree to refrain from sperm donation from check-in through 6 months after dosing.
8. Willing to avoid prolonged sun exposure while taking SMV and through follow-up. Subjects should also be advised to use a broad spectrum sun screen and lip balm of at least sun protection factor (SPF) \> 30 to help protect against potential sunburn.

Exclusion Criteria:

1. Pregnant or nursing (lactating) females, confirmed by a positive HCG laboratory test or females contemplating pregnancy. Men whose female partners are pregnant or contemplating pregnancy from the date of screening until 6 months after their last dose of study drugs.
2. 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.
3. Positive screening test for hepatitis B, C or HIV serology. Subjects previously infected with HCV and achieved a sustained virologic response with treatment (no detectable HCV RNA 6 months post treatment) are eligible.
4. 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.
5. Participation in an investigational drug trial or having received an investigational vaccine within 30 days or 5 half-lives (whichever is longer) prior to study medication.
6. Clinically significant abnormal ECG findings. Particularly, a history or family history of prolonged QT syndrome (e.g., torsade de pointes) or sudden cardiac death.
7. ECG with PR \> 200 ms, QRS \> 120 ms, QTcF \> 450 ms, as assessed by centrally read 12 lead ECG at the screening visit.
8. Clinically significant blood loss or elective blood donation of significant volume (i.e., \> 500 mL) within 60 days of first dose of study drug; \> 1 unit of plasma within 7 days of first dose of study drug.
9. Abnormal heart rate, respiratory rate, temperature or blood pressure values outside of the normal range (evaluated in a semi-recumbent or recumbent position after 5 minutes of rest). One repeat measurement after an additional 5 minutes of rest is permitted.
10. Evidence of active infection.
11. Unwilling to abstain from alcohol for at least 1 week prior to the start of dosing through the study completion visit.
12. History of regular alcohol intake \> 7 units per week of alcohol for females and \> 14 units per week for males (one unit is defined as 10 g alcohol) within 3 months of the screening visit.
13. History of tobacco use or used nicotine-containing products within 3 months of the screening visit.
14. The subject has a positive pre-study drug screen.
15. The use of concomitant medications, including prescription, over the counter medications, herbal medications, inducers or inhibitors of CYP450 enzymes or drug transporters (including P-gp) within 14 days prior to the first dose of study medication is excluded, unless approved by the Sponsor's Medical Monitor. Occasional use of acetaminophen is permitted.
16. Exposure to more than four new investigational entities within 12 months prior to the first dosing day.
17. Hypersensitivity to the active substances or to any of the excipients of AL-335, ACH-3102 or SMV.
18. Subjects of East Asian ancestry.
19. Abnormal biochemistry or hematology laboratory results obtained at screening. Elevated bilirubin in subjects with suspected Gilbert's disease is allowed.
20. Unwillingness or inability to comply with the study protocol for any other reason.

Primary outcomes:
measure: Multiple dose PK Profile, Cmax and AUC: effect of ACH-3102 on AL-335 and metabolites
timeFrame: From screening to Day 28 follow-up visit
measure: Multiple dose PK Profile, Cmax and AUC: effect of Simeprevir on AL-335 and metabolites
timeFrame: From screening to Day 24 visit
measure: Multiple dose PK Profile, Cmax and AUC: effect of ACH-3102 and Simeprevir on AL-335 and metabolites
timeFrame: From screening to Day 28 follow-up visit
Secondary outcomes:
measure: Safety Data: Composite number and frequency of treatment emergent adverse events, physical examination findings, abnormal vital signs, 12 lead ECG and abnormal clinical laboratory results
timeFrame: From screening to Day 28 follow-up visit
measure: Steady-state PK Profile from Clast, t1/2, Tmax, Tlast, CL/F, Vz/F, λz: effect of AL-335 and ACH-3102 on Simeprevir
timeFrame: From screening to Day 28 follow-up visit
measure: Steady-state PK Profile from Clast, t1/2, Tmax, Tlast, CL/F, Vz/F, λz: effect of AL-335 and Simeprevir on ACH-3102
timeFrame: From screening to Day 28 follow-up visit
Other outcomes:
Locations:
city: Rennes
country: France
facility: Biotrial
Study officials:
References:
citation: Valade E, Valenzuela B, Kakuda TN, Westland C, McClure MW, Ouwerkerk-Mahadevan S, Perez-Ruixo JJ, Ackaert O. Characterizing the Pharmacokinetic Interaction Between Simeprevir and Odalasvir in Healthy Volunteers Using a Population Modeling Approach. AAPS J. 2018 Oct 22;20(6):111. doi: 10.1208/s12248-018-0271-0.
citation: Kakuda TN, McClure MW, Westland C, Vuong J, Homery MC, Poizat G, Viguerie L, Denot C, Patat A, Zhang Q, Hui J, Apelian D, Smith DB, Chanda SM, Fry J. Pharmacokinetics, safety, and tolerability of the 2- and 3-direct-acting antiviral combination of AL-335, odalasvir, and simeprevir in healthy subjects. Pharmacol Res Perspect. 2018 Apr 30;6(3):e00395. doi: 10.1002/prp2.395. eCollection 2018 Jun.