Phase 1
Completed N=29
Relative Bioavailability Study of Marketed and Lower Dose Ambrisentan in Healthy Adult Participants
Hypertension, Pulmonary
Source: ClinicalTrials.gov NCT04095286 ↗
Enrolled (actual)
29
Serious AEs
0.0%
Results posted
Aug 2020
Primary outcomePrimary: Maximum Observed Plasma Concentration (Cmax) After Administration of AMB Under Fasted Condition — 359.030; 316.505; 353.252 Nanogram per milliliter
Summary
This is a single center, open-label, randomized, single-dose, three-period cross-over study in healthy participants. The aim of this study is to provide clinically relevant information on the pharmacokinetic (PK) and safety profile of a new lower dose formulation ambrisentan (AMB) tablet, which is intended for pediatric use. The study will compare the relative bioavailability of the lower dose tablet, dispersed in water and administered orally, with the reference marketed AMB tablet in healthy adults. The total study duration for each participant is expected to be approximately 9 weeks.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) After Administration of AMB Under Fasted Condition |
359.030; 316.505; 353.252 | — |
| PRIMARY Time to Cmax (Tmax) After Administration of AMB Under Fasted Condition |
1.000; 2.000; 1.750 | — |
| PRIMARY Time of Last Quantifiable Concentration (Tlast) After Administration of AMB Under Fasted Condition |
72.00; 72.00; 72.00 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [(AUC(0-inf)] After Administration of AMB Under Fasted Condition |
3006.443; 2859.283; 2963.908 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve From Time Zero to Last Time of Quantifiable Concentration [AUC(0-t)] After Administration of AMB Under Fasted Condition |
2844.151; 2849.378; 2779.364 | — |
| PRIMARY Apparent Terminal Phase Half-life (t1/2) After Administration of AMB Under Fasted Condition |
19.250; 18.119; 18.197 | — |
| SECONDARY Number of Participants With Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs >=2%) |
5; 7; 5; 0; 0; 0 | — |
| SECONDARY Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline |
0; 0; 0; 27; 25; 26 | — |
| SECONDARY Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings |
5; 6; 5; 0; 0; 0 | — |
| SECONDARY Number of Participants With Worst Case Hematology Results Relative to PCI Criteria Post-Baseline Relative to Baseline |
0; 0; 0; 27; 25; 26 | — |
| SECONDARY Number of Participants With Worst Case Clinical Chemistry Results Relative to PCI Criteria Post-Baseline Relative to Baseline |
0; 0; 0; 27; 25; 26 | — |
| SECONDARY Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring.
- Average systolic blood pressure between 100-160 millimeter of mercury (mmHg) and diastolic between 55-90 mmHg (inclusive) over 3 readings at Screening.
- Body weight >=50 kilogram (kg) for men and >= 45kg for women, and body mass index (BMI) within the range 18-30 kilogram per meter square (kg/m^2) (inclusive).
- Male participants are eligible to participate if they agree to the following during the study and for at least 13 weeks afterwards corresponding to time needed to eliminate study intervention (5 terminal half-lives) plus an additional 90 days (a spermatogenesis cycle): 1. Refrain from donating sperm plus either 2. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR
- Must agree to use contraception/barrier, as follows: Agree to use a male condom; and Female partner to use an additional highly effective contraceptive method with a failure rate of 1.5 times upper limit of normal (ULN)
- Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin 450 millisecond (msec).
- Past or intended use of over-the-counter or prescription medication (including vitamins and dietary or herbal supplements but excluding paracetamol 14 units. One unit is equivalent to 8 grams of alcohol: a half-pint (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- Smoking > 5 cigarettes per week (or equivalent) and participants must be able to abstain from smoking for a 24-hour period prior to dose and any time whilst in the clinical unit.
- Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study
Data sourced from ClinicalTrials.gov (NCT04095286). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.