A Study to Evaluate the Cardiac Safety of a Single Dose of AL-335 Administered on a Background of Simeprevir and Odalasvir and of Repeated Doses of Odalasvir Administered Alone in Healthy Participants

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: AL-335 1200 mg; Drug: ODV Placebo (Matching 125 mg ODV); Drug: ODV 200 mg; Drug: ODV Placebo (Matching 200 mg ODV); Drug: ODV Placebo (Matching 25 mg ODV); Drug: SMV 150 mg; Drug: ODV 100 mg; Drug: ODV 25 mg; Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin); Drug: SMV Placebo (Matching 150 mg SMV); Drug: ODV 125 mg; Drug: AL-335 Placebo (matching 1200 mg AL-335); Drug: ODV Placebo (Matching 100 mg ODV)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03155893

64294178HPC1012 (Other Identifier)

CR108332

Details and patient eligibility

About

The main purpose of this study is to assess the effect of a single supratherapeutic dose of AL-335 administered on top of multiple doses of odalasvir (ODV) and simeprevir (SMV) versus placebo on QT/QT interval corrected for heart rate (QTc) interval changes, using intersection-union test (IUT) analysis (Panel 1); to assess the effect of ODV on QT/QTc and PR interval changes after multiple supratherapeutic doses of ODV using an exposure-response (ER) approach (Panel 2); and to assess the effect of multiple supratherapeutic doses of ODV on echocardiographic left ventricular ejection fraction (LVEF) (Panel 2) in healthy participants.

Enrollment: 59 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participants must sign and date an informed consent form (ICF) indicating that he or she understands the purpose of, and the procedures required for, the study and is willing to participate in the study
• Participant must be healthy on the basis of physical examination, medical history, vital signs, and laboratory tests performed at screening
• Participant must have a blood pressure (supine after at least 5 minutes rest) between 90 and 140 millimeters of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic
• Participant must have a 12-lead electrocardiogram (ECG) (based on the mean value of triplicate ECG parameters) consistent with normal cardiac conduction and function at screening
• Participant must have an echocardiogram at screening with left ventricular ejection fraction (LVEF) greater than or equal to (>=)55 percent (%). Participant should not have any other echocardiogram finding suggestive of clinically relevant cardiomyopathy
• Female participant must have a negative highly sensitive urine pregnancy test at Day -2 (Panel 1) or Day -4 (Panel 2)

Exclusion criteria

• Participant has a history of liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, constipation, or gastrointestinal surgery that in the investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
• Participant with a history of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardia, and heart blocks
• Participant with unusual T-wave morphology (such as bifid T-wave) likely to interfere with corrected QT (QTc) measurements
• Participant with a past history of sick sinus syndrome, heart arrhythmias (example, extrasystolic rhythms or tachycardia at rest). Isolated extrasystolic beats are not exclusionary; risk factors associated with Torsade de Pointes (TdP) such as hypokalemia; family history of short/long QT syndrome; sudden unexplained death (including sudden infant death syndrome in a first-degree relative [that is, sibling, offspring, or biological parent])
• Participant with any skin condition likely to interfere with electrocardiogram (ECG) electrode placement or adhesion
• Participant with a breast implant or a history of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

59 participants in 5 patient groups, including a placebo group

Panel 1: Treatment A

Experimental group

Description:

Participants will receive odalasvir (ODV) placebo (matching 25 milligram \[mg\] ODV \[1\*25 mg tablet\]) and simeprevir (SMV) placebo (matching 150 mg SMV \[2\*75 mg capsules\]) once daily from Day 1 to 16 along with single dose of AL-335 placebo (matching 1200 milligram \[mg\] AL-335 \[3\*400 mg tablets\]) on Day 15 and moxifloxacin placebo (matching 400 mg moxifloxacin \[1\*400 mg capsule\]) as a single dose on Day 1, 15 and 16 along with moxifloxacin 400 mg (1\*400 mg capsule) single dose on Day 2 orally under fed conditions.

Treatment:

Drug: ODV Placebo (Matching 25 mg ODV)

Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin)

Drug: AL-335 Placebo (matching 1200 mg AL-335)

Drug: SMV Placebo (Matching 150 mg SMV)

Panel 1: Treatment B

Experimental group

Description:

Participants will receive odalasvir (ODV) placebo (matching 25 milligram \[mg\] ODV \[1\*25 mg tablet\]) and simeprevir (SMV) placebo (matching 150 mg SMV \[2\*75 mg capsules\]) once daily from Day 1 to 16 along with single dose of AL-335 placebo (matching 1200 milligram \[mg\] AL-335 \[3\*400 mg tablets\]) on Day 15 and moxifloxacin placebo (matching 400 mg moxifloxacin \[1\*400 mg capsule\]) as a single dose on Day 1, 2 and 15 along with moxifloxacin 400 mg (1\*400 mg capsule) single dose on Day 16 orally under fed conditions.

Treatment:

Drug: ODV Placebo (Matching 25 mg ODV)

Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin)

Drug: AL-335 Placebo (matching 1200 mg AL-335)

Drug: SMV Placebo (Matching 150 mg SMV)

Panel 1: Treatment C

Experimental group

Description:

Participants will receive odalasvir (ODV) placebo (matching 25 milligram \[mg\] ODV \[1\*25 mg tablet\]) and simeprevir (SMV) placebo (matching 150 mg SMV \[2\*75 mg capsules\]) once daily on Day 1 and moxifloxacin placebo (matching 400 mg moxifloxacin \[1\*400 mg capsule\]) as a single dose on Day 1, 2, 15 and 16 along with ODV 25 mg (1\*25 mg tablet) and SMV 150 mg (2\*75 mg capsule) once daily on Day 2 to 16 and AL-335 1200 mg (3\*400 mg tablet) single dose on Day 15 orally under fed conditions.

Treatment:

Drug: ODV Placebo (Matching 25 mg ODV)

Drug: AL-335 1200 mg

Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin)

Drug: SMV Placebo (Matching 150 mg SMV)

Drug: SMV 150 mg

Drug: ODV 25 mg

Panel 2: Treatment E

Placebo Comparator group

Description:

Participants will receive ODV placebo (matching 200 mg ODV \[4\*50 mg tablets\]) on Days 1 and 2; ODV placebo (matching 125 mg ODV \[2\*50 mg tablets + 1\*25 mg tablets\]) on Days 3 to 7; and ODV placebo (matching 100 mg ODV \[2\*50 mg tablets\] on Days 8 to 14, orally once daily under fed conditions.

Treatment:

Drug: ODV Placebo (Matching 200 mg ODV)

Drug: ODV Placebo (Matching 125 mg ODV)

Drug: ODV Placebo (Matching 100 mg ODV)

Panel 2: Treatment F

Experimental group

Description:

Participants will receive ODV 200 mg (4\*50 mg tablets) on Days 1 and 2; ODV 125 mg (2\*50 mg tablets + 1\*25 mg tablets) on Days 3 to 7, and ODV 100 mg (2\*50 mg tablets) on Days 8 to 14, orally once daily under fed conditions.

Treatment:

Drug: ODV 125 mg

Drug: ODV 200 mg

Drug: ODV 100 mg