Clinical trial NCT02126956: Mass Balance, Pharmacokinetics, and Metabolism of 14C-labeled ACT-128800 Administered to Healthy Male Subjects
Official title: Single-center, Open-label Study With 14C-labeled ACT-128800 to Investigate the Mass Balance, Pharmacokinetics, and Metabolism Following Single Oral Administration to Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Keywords: ACT-128800
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2014-04-30
Enrollment: 6
Sex: MALE
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The study was conducted to investigate the metabolism and mass balance of ACT-128800, and to identify the elimination pathways (metabolism and excretion) of ACT-128800 and compare them with the known metabolic profiles of ACT-128800 in animals.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent prior to any study-mandated procedure.
* Male and aged between 45 and 65 years (inclusive) at screening.
* No clinically significant findings on physical examination performed at screening.
* Body mass index (BMI) between 18-28 kg/m\^2 (inclusive) at screening.
* Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and heart rate 55-90 bpm (inclusive), measured on the leading arm, after 5 minutes in the supine position at screening. These criteria should also be met before the administration of the first dose.
* 12-lead electrocardiogram without clinically relevant abnormalities at screening.
* Clinical chemistry, hematology, and urinalysis results not deviating from the normal range to a clinically relevant extent at screening.
* Negative results from urine drug screen at screening.
* Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.

Exclusion Criteria:

* Known hypersensitivity to any excipients of the drug formulation.
* Treatment with another investigational drug within the 3 months prior to screening.
* History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
* Excessive caffeine consumption, defined as ≥ 800 mg per day at screening.
* History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drug.
* Smoking within the 3 months prior to screening.
* Any immunosuppressive treatment within 6 weeks before study drug administration.
* Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to screening.
* Loss of 250 mL or more of blood within the 3 months prior to screening.
* Lymphopenia (\< 1,100 lymphocytes/μL).
* Viral, fungal, bacterial or protozoal infection within 4 weeks before study drug administration.
* Positive hepatitis B or hepatitis C serology, except for vaccinated subjects, at screening.
* Positive human immunodeficiency virus serology at screening.
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
* Legal incapacity or limited legal capacity at screening.
* Exposure to artificial ionizing radiation (e.g., X-ray, thyroid scan, study with radiolabeled compound) in the 12-month period before screening.
* A history of clinically relevant constipation (defined as lasting more than 3 days) in the 4-week period before screening.

Primary outcomes:
measure: Cumulative recovery of total radioactivity expressed as a percentage of the administered dose (mass balance) in the urine
timeFrame: Up to end of study, approximately 240 hours
measure: Cumulative recovery of total radioactivity expressed as a percentage of the administered dose (mass balance) in the faeces
timeFrame: Up to end of study, approximately 240 hours
Secondary outcomes:
measure: Maximum concentration (Cmax) of 14C-radioactivity in whole blood
timeFrame: Up to end of study, approximately 240 hours
measure: Time to maximum concentration (tmax) of 14C-radioactivity in whole blood
timeFrame: Up to end of study, approximately 240 hours
measure: Area under the plasma concentration-time curve (AUC(0-t)) of 14C-radioactivity in whole blood
timeFrame: Up to end of study, approximately 240 hours
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of 14C-radioactivity in whole blood
timeFrame: Up to end of study, approximately 240 hours
measure: Half life (t1/2) of 14C-radioactivity in whole blood
timeFrame: Up to end of study, approximately 240 hours
measure: Maximum concentration (Cmax) of 14C-radioactivity in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Time to maximum concentration (tmax) of 14C-radioactivity in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Area under the plasma concentration-time curve (AUC(0-t)) of 14C-radioactivity in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of 14C-radioactivity in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Half life (t1/2) of 14C-radioactivity in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Maximum concentration (Cmax) of ACT-12880 in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Time to maximum concentration (tmax) of ACT-12880 in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Area under the plasma concentration-time curve (AUC(0-t)) of ACT-12880 in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of ACT-12880 in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Half life (t1/2) of ACT-12880 in plasma
timeFrame: Up to end of study, approximately 240 hours
measure: Total lymphocyte count
timeFrame: Up to end of study, approximately 240 hours
measure: Change in systolic blood pressure from baseline up to end of study
timeFrame: Up to end of study, approximately 240 hours
measure: Change in diastolic blood pressure from baseline up to end of study
timeFrame: Up to end of study, approximately 240 hours
measure: Change in heart rate from baseline up to end of study
timeFrame: Up to end of study, approximately 240 hours
measure: Change in body temperature from baseline up to end of study
timeFrame: Up to end of study, approximately 240 hours
measure: Change in body weight from baseline to end of study
timeFrame: Up to end of study, approximately 240 hours
Other outcomes:
Locations:
city: Allschwil
country: Switzerland
facility: Swiss Pharma Contract
Study officials:
affiliation: Actelion
name: Patrick Brossard, PhD
role: STUDY_DIRECTOR
References: