Study to Evaluate the Effect of ALS-008176 on Cardiac Repolarization Interval in Healthy Participants

NCT02833831 | Completed Phase 1

• 2 other identifiers: CR10816964041575RSV1003
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to evaluate the effect of supratherapeutic exposures of ALS-008176 on the QT/ corrected QT interval (QTc) interval in healthy participants (Panel 2).

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Corrected QT intervals (QTc)

  Change from baseline in QTc intervals with Fredericia correction will be analyzed.

  Baseline up to Day 2

Secondary Outcomes (15)

• Number of participants with adverse events as a measure of safety and tolerability

  10 to 14 days after last study drug intake

• Change from baseline in ECG parameters: RR interval, PR interval and QRS interval

  Baseline up to Day 2

• ALS-008112 and ALS 008144 plasma concentration-effect relationship for changes in QT/QTc (Panels 1 and 2)

  up to Day 15 in Panel 1; up to Day 2 in Panel 2

• Change from Baseline in QT/QTc interval in healthy subjects (Panel 2)

  up to Day 2

• Maximum Observed Plasma Concentration (Cmax)

  up to Day 15 in Panel 1; up to Day 2 in Panel 2

Study Arms (9)

Part 1: Group 1

EXPERIMENTAL

Participants will receive Treatment A (a single dose of ALS-008176 1,500 mg) or Treatment B (a single dose of placebo) under fasted conditions.

Drug: ALS-008176; Drug: Placebo

Part 1: Group 2

EXPERIMENTAL

Participants will receive Treatment C (a single dose of ALS-008176 2,500 mg) or Treatment D (a single dose of placebo) under fasted conditions.

Drug: ALS-008176; Drug: Placebo

Part 1: Group 3

EXPERIMENTAL

Participants will receive Treatment E (a single dose of ALS-008176 3,000 mg) or Treatment F (a single dose of placebo) under fasted conditions.

Drug: ALS-008176; Drug: Placebo

Part 2: Sequence GHI

EXPERIMENTAL

Participants will receive Treatment G (a single dose of ALS-008176 3,000 mg + a single dose of moxifloxacin placebo under fasted conditions) then Treatment H (a single dose of ALS-008176 placebo + a single dose of moxifloxacin 400 mg under fasted conditions) then Treatment I (a single dose of ALS-008176 placebo + a single dose of moxifloxacin placebo under fasted conditions). There will be a washout period of at least 14 days between subsequent treatments.

Drug: ALS-008176; Drug: Placebo; Drug: Moxifloxacin

Part 2: Sequence HIG

EXPERIMENTAL

Participants will receive Treatment H then Treatment I and then Treatment G. There will be a washout period of at least 14 days between subsequent treatments.

Drug: ALS-008176; Drug: Placebo; Drug: Moxifloxacin

Part 2: Sequence IGH

EXPERIMENTAL

Participants will receive Treatment I then Treatment G and then Treatment H. There will be a washout period of at least 14 days between subsequent treatments.

Drug: ALS-008176; Drug: Placebo; Drug: Moxifloxacin

Part 2: Sequence IHG

EXPERIMENTAL

Participants will receive Treatment I then Treatment H and then Treatment G. There will be a washout period of at least 14 days between subsequent treatments.

Drug: ALS-008176; Drug: Placebo; Drug: Moxifloxacin

Part 2: Sequence HGI

EXPERIMENTAL

Participants will receive Treatment H then Treatment G and then Treatment I. There will be a washout period of at least 14 days between subsequent treatments.

Drug: ALS-008176; Drug: Placebo; Drug: Moxifloxacin

Part 2: Sequence GIH

EXPERIMENTAL

Participants will receive Treatment G then Treatment I and then Treatment H. There will be a washout period of at least 14 days between subsequent treatments.

Drug: ALS-008176; Drug: Placebo; Drug: Moxifloxacin

Interventions

ALS-008176 DRUG

Participants will receive a single dose of ALS-008176 orally.

Part 1: Group 1; Part 1: Group 2; Part 1: Group 3; Part 2: Sequence GHI; Part 2: Sequence GIH; Part 2: Sequence HGI; Part 2: Sequence HIG; Part 2: Sequence IGH; Part 2: Sequence IHG

Placebo DRUG

Matching Placebo will be administered.

Part 1: Group 1; Part 1: Group 2; Part 1: Group 3; Part 2: Sequence GHI; Part 2: Sequence GIH; Part 2: Sequence HGI; Part 2: Sequence HIG; Part 2: Sequence IGH; Part 2: Sequence IHG

Moxifloxacin DRUG

Participants will receive a single dose of moxifloxacin 400 mg.

Part 2: Sequence GHI; Part 2: Sequence GIH; Part 2: Sequence HGI; Part 2: Sequence HIG; Part 2: Sequence IGH; Part 2: Sequence IHG

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 is willing to participate in the study
• Participant must be willing and able to adhere to the prohibitions and restrictions specified in protocol
• A female participant must be of non-childbearing potential, defined as either: a) Postmenopausal- A postmenopausal state is defined as no menses for at least 12 months without an alternative medical cause and a serum follicle stimulating hormone (FSH) level in the postmenopausal range (\> 40 International units per liter \[IU/L\] or International units/milliliter \[mIU/mL\]); b) Permanently sterile- Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures (without reversal operation), and bilateral oophorectomy
• During the study and for a minimum of one spermatogenesis cycle (defined as approximately 90 days) after receiving the (last dose of) study drug, a male participant: a) who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (example, condom with spermicidal foam/gel/film/cream/suppository); b) who is sexually active with a pregnant woman must use a condom; c) must agree not to donate sperm
• Female partners of male participants must either be surgically sterilized, postmenopausal (amenorrhea for a minimum of 1 year) or, if of childbearing potential, must agree to use at least one of the following contraceptive methods for 90 days following the last dose of study drug: a nonhormonal intrauterine device with spermicide; contraceptive sponge with spermicide, diaphragm with spermicide, cervical cap with spermicide, or oral, implantable, transdermal, or injectable hormonal contraceptives
• A female participant must have a negative serum beta human chorionic gonadotropin (b-hCG) pregnancy test at screening and on Day -1
• A female participant must agree not to donate eggs (ova, oocytes) during the study and for at least 90 days after receiving the (last dose of) study drug
• Participants must have a body mass index (BMI); weight (kilogram \[kg\])/height\^2 (meter \[m\]\^2) between 18.0 and 30.0 kg/m\^2 (inclusive) at screening
• Participants 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 at screening
• Participants must have a 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and function at screening, including: a) Sinus rhythm (heart rate between 45 and 100 beats per minute (bpm), inclusive); b) QT interval corrected for heart rate according to Fridericia (QTcF) interval between 350 milliseconds (ms) and 430 ms for male participants, and between 350 ms and 450 ms for female participants (inclusive); c) QRS interval of \<110 ms; d) PR interval \<=200 ms; e) Morphology consistent with healthy cardiac conduction and function
• Participants must be non-smokers for at least 3 months prior to screening
• Participants must be healthy on the basis of a medical evaluation that reveals the absence of any clinically significant abnormality and includes a complete physical examination, medical and surgical history, vital signs, ECGs, and the results of blood biochemistry and hematology tests and a urinalysis performed at screening. If there are abnormalities the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the Investigator
• Participants must have normal values for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (\<= 1.0\*upper limit of laboratory normal range \[ULN\])

You may not qualify if:

• Participants 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
• Participants with one or more laboratory abnormalities at screening as defined in the Protocol
• Participants with a history of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardias, heart blocks and incomplete and complete right and left bundle branch blocks
• Participants with unusual T wave morphology (such as bifid T wave) likely to interfere with QTc measurements
• Participants with a past history of heart arrhythmias (extra systolic beats or tachycardia at rest) or with a history of risk factors for Torsade de Pointes syndrome (for example, hypokalemia or family history of short/long QT syndrome, or sudden unexplained death at a young age \[less than or equal to 40 years\], drowning or sudden infant death in a first degree relative \[that is, sibling, offspring, or biological parent\])
• Participants with electrolyte abnormalities (hypokalemia, hypocalcemia, hypomagnesemia) of grade 2 or above within 21 days prior to the (first) intake of the study drug
• Participants with any skin condition likely to interfere with ECG electrode placement or adhesion
• Participants with a breast implant or a history of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues
• Participants with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
• Participants with a history of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy diagnosed in previous studies with experimental drugs
• Participants with presence of any febrile illness or symptoms of upper or lower respiratory tract infection in the 14 days before the (first) administration of study drugs
• Participant has taken any disallowed therapies as noted in Concomitant Therapy before the planned (first) intake of study drug
• Participant has a history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria within 5 years before screening or positive test result(s) for alcohol and/or drugs of abuse (including barbiturates, opiates, cocaine, amphetamines, methadone, benzodiazepines, methamphetamine, tetrahydrocannabinol, phencyclidine, and tricyclic antidepressants) at screening
• Participant has known allergies, hypersensitivity, or intolerance to ALS-008176, moxifloxacin or its excipients
• Participant has known allergy to heparin or history of heparin-induced thrombocytopenia

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Unknown Facility

Tempe, Arizona, United States

Location

MeSH Terms

Interventions

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

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: June 21, 2016
• First Posted: July 14, 2016
• Study Start: June 2, 2016
• Primary Completion: February 17, 2017
• Study Completion: February 24, 2017
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

US (1)