A Thorough QT Study of Aticaprant (JNJ-67953964) in Healthy Adult Participants
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Drug: Aticaprant Supratherapeutic DoseDrug: Aticaprant Therapeutic DoseDrug: Placebo
- Registration Number
- NCT05387759
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to assess the effects of aticaprant on QT/ QT interval corrected for heart rate (HR) (QTc) intervals and electrocardiogram (ECG) morphology at therapeutic and supratherapeutic exposures in healthy adult participants.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Inclusion Criteria
- Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and admission to the study center on Day -1 of the first treatment period. Minor abnormalities in ECG, which are not considered to be of clinical significance by the investigator, are acceptable
- Body mass index (BMI; weight [kilograms {kg}/ height square [meter square {m^2}]) between 18 and 30.0 kg/m^2 (inclusive), and body weight not less than 50 kg at screening
- All female participants must have a negative serum pregnancy test (Beta-human chorionic gonadotropin [Beta-hCG]) at screening and a negative urine pregnancy test at admission to the study site on Day -1 of the first treatment period
- A woman must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of at least 90 days after receiving the last dose of study intervention
- Non-smoker (not smoked for 3 months prior to screening)
Exclusion Criteria
- History of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, lipid abnormalities, bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, Parkinson's disease, infection, or any other illness that the investigator considers should exclude the participant
- History of additional risk factors for Torsade de Pointes or the presence of a family history of short QT syndrome, long QT syndrome, sudden unexplained death at a young age (less than/equal to 40 years), drowning or sudden infant death syndrome in a first degree relative (that is, biological parent, sibling, or child)
- Any skin condition likely to interfere with electrocardiographic electrode placement or adhesion
- Breast implant or a history of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues
- History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence 3 Aticaprant Therapeutic Dose Healthy participants will receive single oral dose of Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3 and then Treatment A in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 3 Placebo Healthy participants will receive single oral dose of Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3 and then Treatment A in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 2 Aticaprant Therapeutic Dose Healthy participants will receive single oral dose of Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2, followed by Treatment C in Treatment Period 3 and then Treatment D in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 4 Aticaprant Supratherapeutic Dose Healthy participants will receive single oral dose of Treatment D in Treatment Period 1, followed by Treatment C in Treatment Period 2, followed by Treatment A in Treatment Period 3 and then Treatment B in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7 to 15 days between each treatment period. Treatment Sequence 1 Aticaprant Supratherapeutic Dose Healthy participants will receive single oral dose of Aticaprant (Dose 1) (Treatment A) in Treatment Period 1, followed by Moxifloxacin (Dose 2) (Treatment D) in Treatment Period 2, followed by Aticaprant (Dose 3) (Treatment B) in Treatment Period 3 and then placebo (Treatment C) in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 4 Aticaprant Therapeutic Dose Healthy participants will receive single oral dose of Treatment D in Treatment Period 1, followed by Treatment C in Treatment Period 2, followed by Treatment A in Treatment Period 3 and then Treatment B in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7 to 15 days between each treatment period. Treatment Sequence 1 Aticaprant Therapeutic Dose Healthy participants will receive single oral dose of Aticaprant (Dose 1) (Treatment A) in Treatment Period 1, followed by Moxifloxacin (Dose 2) (Treatment D) in Treatment Period 2, followed by Aticaprant (Dose 3) (Treatment B) in Treatment Period 3 and then placebo (Treatment C) in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 1 Placebo Healthy participants will receive single oral dose of Aticaprant (Dose 1) (Treatment A) in Treatment Period 1, followed by Moxifloxacin (Dose 2) (Treatment D) in Treatment Period 2, followed by Aticaprant (Dose 3) (Treatment B) in Treatment Period 3 and then placebo (Treatment C) in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 2 Aticaprant Supratherapeutic Dose Healthy participants will receive single oral dose of Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2, followed by Treatment C in Treatment Period 3 and then Treatment D in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 2 Placebo Healthy participants will receive single oral dose of Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2, followed by Treatment C in Treatment Period 3 and then Treatment D in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 3 Aticaprant Supratherapeutic Dose Healthy participants will receive single oral dose of Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3 and then Treatment A in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 4 Moxifloxacin Healthy participants will receive single oral dose of Treatment D in Treatment Period 1, followed by Treatment C in Treatment Period 2, followed by Treatment A in Treatment Period 3 and then Treatment B in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7 to 15 days between each treatment period. Treatment Sequence 4 Placebo Healthy participants will receive single oral dose of Treatment D in Treatment Period 1, followed by Treatment C in Treatment Period 2, followed by Treatment A in Treatment Period 3 and then Treatment B in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7 to 15 days between each treatment period. Treatment Sequence 1 Moxifloxacin Healthy participants will receive single oral dose of Aticaprant (Dose 1) (Treatment A) in Treatment Period 1, followed by Moxifloxacin (Dose 2) (Treatment D) in Treatment Period 2, followed by Aticaprant (Dose 3) (Treatment B) in Treatment Period 3 and then placebo (Treatment C) in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 2 Moxifloxacin Healthy participants will receive single oral dose of Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2, followed by Treatment C in Treatment Period 3 and then Treatment D in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period. Treatment Sequence 3 Moxifloxacin Healthy participants will receive single oral dose of Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, followed by Treatment D in Treatment Period 3 and then Treatment A in Treatment Period 4, on Day 1 of each treatment period. There will be a wash-out period up to 7-15 days between each treatment period.
- Primary Outcome Measures
Name Time Method Change from Baseline in QTc at Each Time Point Baseline up to Day 4 Change from baseline in QTc at each time point will be reported.
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) Up to Day 4 Number of participants with AEs will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product.
Time To Reach The Maximum Observed Concentration of Aticaprant (Tmax) Predose up to 72 hours postdose (up to Day 4) Tmax is the actual sampling time to reach the maximum observed plasma concentration of aticaprant.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time of Aticaprant (AUC[0-infinity]) Predose up to 72 hours postdose (up to Day 4) AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time of aticaprant.
Area Under the Plasma Concentration-Time Curve From Time Zero to last of Aticaprant (AUC [0-last]) Predose up to 72 hours postdose (up to Day 4) AUC (0-last) is the area under the plasma concentration-time curve from time 0 to the time of the last measurable (non-below quantification limit) concentration of aticaprant.
Number of Participants With Change in Vital Signs Up to Day 4 Number of participants with change in vital signs will be reported. Body temperature, blood pressure, and pulse/heart rate (HR) measurements will be assessed.
Maximum Observed Concentration (Cmax) of Aticaprant Predose up to 72 hours postdose (up to Day 4) Cmax is defined as the maximum observed plasma concentration of aticaprant and it's metabolite.
Number of Participants With Change in Laboratory Values Up to Day 4 Number of participants with change in laboratory parameters will be reported. Hematology, serum chemistry, and routine urinalysis will be assessed.
Number of Participants with AEs of Special Interest (AESI) Up to Day 4 Number of participants with AESIs will be reported. Pruritus and severe diarrhea is considered to be an AESI.
Trial Locations
- Locations (1)
Clinical Pharmacology Unit
🇧🇪Merksem, Belgium