search
Back to results

A Study of Single and Multiple Doses of Different Formulations of a Prostacyclin Receptor Agonist

Primary Purpose

Pulmonary Arterial Hypertension

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Prostacyclin Receptor Agonist
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Otherwise, healthy as deemed by the investigator on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiograms (ECG) performed at Screening and Day -1 of oral treatment period
  • Otherwise, healthy medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, blood coagulation, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator
  • Body mass index (BMI) within the range 18.0 to 32.0 kilograms per meter square (kg/m^2) (inclusive) and body weight not less than 50 kilograms (kg) at screening
  • All female participants must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening
  • A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study intervention

Exclusion Criteria:

  • Known allergies, hypersensitivity, anaphylaxis, or intolerance to prostacyclin receptor agonist or drugs of the same class, or any excipient (including poloxamer and polysorbate) of the drug formulation(s)
  • Clinically significant abnormal physical examination, vital signs, or 12-lead ECG (QTc greater than or equal to [>=]450 milliseconds [msec] for men and >=460 msec for women. QT corrected according to Bazett's formula [QTcB]) as assessed by the Investigator at Screening or Day -1 of oral treatment period
  • History of malignancy within 3 years before screening (exceptions are squamous and basal cell carcinomas of the skin
  • Positive serologic testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), active coronavirus disease 2019 (COVID-19) infection
  • A history of repeated (more than once over the last 30 days) fainting due to cardiac cause, collapse, syncope, orthostatic hypotension, or vasovagal reactions

Sites / Locations

  • CelerionRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Prostacyclin Receptor Agonist

Arm Description

Participants in Cohort 1-6 will receive multiple doses of prostacyclin receptor agonist of formulation 1 in treatment period 1, followed by a single dose of various other formulations (formulation 2, 3, and 4) in treatment period 2. Cohorts 4, 5, and 6 will be optional with dose based on PK, safety and tolerability data of previous 3 cohorts (preceding cohorts).

Outcomes

Primary Outcome Measures

Number of Participants with Treatment-emergent Adverse Events (TEAEs)
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.
Number of Participants With Serious TEAEs
A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Serious TEAEs are defined as serious events between administration of study drug and after the last dose that were absent before treatment or that worsen relative to pretreatment state.
Number of Participants with TEAEs by Severity
Number of participants with TEAEs by severity will be evaluated. An assessment of severity grade will be made using the following general categorical descriptors, such as Mild (Awareness of symptoms that are easily tolerated, causing minimal discomfort, and not interfering with everyday activities), Moderate (Sufficient discomfort is present to cause interference with normal activity), and Severe (Extreme distress, causing significant impairment of functioning or incapacitation, and prevents normal everyday activities).
Number of Participants with TEAEs Leading to Discontinuation
Number of participants with TEAEs leading to discontinuation will be reported.
Number of Participants With Change from Baseline in Clinical Laboratory Values
Number of participants with change from baseline in clinical laboratory values (chemistry, hematology, and urinalysis) will be evaluated.
Number of Participants With Injection Site Reactions
Number of participants with injection site reactions will be evaluated.

Secondary Outcome Measures

Treatment Period 1: Maximum Observed Plasma Concentration of Prostacyclin Receptor Agonist at Steady State (Cmax[ss])
Cmax(ss) is the maximum observed plasma concentration of prostacyclin receptor agonist at steady state, during treatment period 1.
Treatment Period 1: Time to Reach Maximum Observed Plasma Concentration of Prostacyclin Receptor Agonist at Steady State (Tmax[ss])
Tmax(ss) is the actual sampling time to reach maximum observed plasma concentration of prostacyclin receptor agonist at steady state, during treatment period 1.
Treatment Period 1: Area Under the Curve From Time Zero to tau of Prostacyclin Receptor Agonist at Steady State (AUC[0-tau{ss}])
AUC(0-tau[ss]) is defined as area under the curve from time 0 to tau hours post dose of prostacyclin receptor agonist at steady state, during treatment period 1.
Treatment Period 1: Plasma Concentration at the End of One Dose Interval of Prostacyclin Receptor Agonist at Steady State (Ctrough[ss])
Ctrough(ss) is the plasma concentration at the end of one dose interval of prostacyclin receptor agonist at steady state, during treatment period 1.
Treatment Period 2: Maximum Observed Plasma Concentration (Cmax) of Prostacyclin Receptor Agonist
Cmax is the maximum observed plasma concentration of prostacyclin receptor agonist, during treatment period 2.
Treatment Period 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Prostacyclin Receptor Agonist
Tmax is the actual sampling time to reach maximum observed plasma concentration of prostacyclin receptor agonist, during treatment period 2.
Treatment Period 2: Area Under the Plasma Concentration-time Curve from time Zero to time t (AUC[0-t]) of Prostacyclin Receptor Agonist
Area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of concentration of prostacyclin receptor agonist, during treatment period 2.
Treatment Period 2: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Prostacyclin Receptor Agonist
AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/ lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration of prostacyclin receptor agonist, and lambda (z) is elimination rate constant, during treatment period 2.
Treatment Period 2: Area Under the Plasma Concentration-time Curve From Zero to Time 24 Hours (AUC [0-24h]) of Prostacyclin Receptor Agonist
AUC (0-24h) is the area under the plasma concentration-time curve from zero to time 24 hours, during treatment period 2.
Treatment Period 2: Area Under the Plasma Concentration-time Curve From Zero to Day 14 (AUC [0-Day 14]) of Prostacyclin Receptor Agonist
AUC (0-Day 14) is the area under the plasma concentration-time curve from zero to Day 14, during treatment period 2.
Treatment Period 2: Area Under the Plasma Concentration-time Curve From Zero to Day 28 (AUC [0-Day 28]) of Prostacyclin Receptor Agonist
AUC (0-Day 28) is the area under the plasma concentration-time curve from zero to Day 28, during treatment period 2.
Treatment Period 2: Plasma Concentration of Prostacyclin Receptor Agonist at Day 14 (C[Day 14])
C(Day 14) is the plasma concentration of prostacyclin receptor agonist at Day 14, during treatment period 2
Treatment Period 2: Plasma Concentration of Prostacyclin Receptor Agonist at Day 28 (C[Day 28])
C(Day 28) is the plasma concentration of prostacyclin receptor agonist at Day 28, during treatment period 2.

Full Information

First Posted
June 16, 2022
Last Updated
September 12, 2023
Sponsor
Actelion
search

1. Study Identification

Unique Protocol Identification Number
NCT05427162
Brief Title
A Study of Single and Multiple Doses of Different Formulations of a Prostacyclin Receptor Agonist
Official Title
Open-Label, Randomized Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of Different Formulations of an IP Receptor Agonist
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 21, 2022 (Actual)
Primary Completion Date
November 13, 2023 (Anticipated)
Study Completion Date
November 13, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to assess safety and tolerability of prostacyclin receptor agonist formulation in treatment period 1 and with different formulation of prostacyclin receptor agonist in treatment period 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
136 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Prostacyclin Receptor Agonist
Arm Type
Experimental
Arm Description
Participants in Cohort 1-6 will receive multiple doses of prostacyclin receptor agonist of formulation 1 in treatment period 1, followed by a single dose of various other formulations (formulation 2, 3, and 4) in treatment period 2. Cohorts 4, 5, and 6 will be optional with dose based on PK, safety and tolerability data of previous 3 cohorts (preceding cohorts).
Intervention Type
Drug
Intervention Name(s)
Prostacyclin Receptor Agonist
Intervention Description
Prostacyclin receptor agonist will be administered.
Primary Outcome Measure Information:
Title
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Description
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.
Time Frame
Up to 114 days
Title
Number of Participants With Serious TEAEs
Description
A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Serious TEAEs are defined as serious events between administration of study drug and after the last dose that were absent before treatment or that worsen relative to pretreatment state.
Time Frame
Up to 114 days
Title
Number of Participants with TEAEs by Severity
Description
Number of participants with TEAEs by severity will be evaluated. An assessment of severity grade will be made using the following general categorical descriptors, such as Mild (Awareness of symptoms that are easily tolerated, causing minimal discomfort, and not interfering with everyday activities), Moderate (Sufficient discomfort is present to cause interference with normal activity), and Severe (Extreme distress, causing significant impairment of functioning or incapacitation, and prevents normal everyday activities).
Time Frame
Up to 114 days
Title
Number of Participants with TEAEs Leading to Discontinuation
Description
Number of participants with TEAEs leading to discontinuation will be reported.
Time Frame
Up to 114 days
Title
Number of Participants With Change from Baseline in Clinical Laboratory Values
Description
Number of participants with change from baseline in clinical laboratory values (chemistry, hematology, and urinalysis) will be evaluated.
Time Frame
Up to 114 days
Title
Number of Participants With Injection Site Reactions
Description
Number of participants with injection site reactions will be evaluated.
Time Frame
Up to 114 days
Secondary Outcome Measure Information:
Title
Treatment Period 1: Maximum Observed Plasma Concentration of Prostacyclin Receptor Agonist at Steady State (Cmax[ss])
Description
Cmax(ss) is the maximum observed plasma concentration of prostacyclin receptor agonist at steady state, during treatment period 1.
Time Frame
Up to 114 days
Title
Treatment Period 1: Time to Reach Maximum Observed Plasma Concentration of Prostacyclin Receptor Agonist at Steady State (Tmax[ss])
Description
Tmax(ss) is the actual sampling time to reach maximum observed plasma concentration of prostacyclin receptor agonist at steady state, during treatment period 1.
Time Frame
Up to 114 days
Title
Treatment Period 1: Area Under the Curve From Time Zero to tau of Prostacyclin Receptor Agonist at Steady State (AUC[0-tau{ss}])
Description
AUC(0-tau[ss]) is defined as area under the curve from time 0 to tau hours post dose of prostacyclin receptor agonist at steady state, during treatment period 1.
Time Frame
Up to 114 days
Title
Treatment Period 1: Plasma Concentration at the End of One Dose Interval of Prostacyclin Receptor Agonist at Steady State (Ctrough[ss])
Description
Ctrough(ss) is the plasma concentration at the end of one dose interval of prostacyclin receptor agonist at steady state, during treatment period 1.
Time Frame
Up to 114 days
Title
Treatment Period 2: Maximum Observed Plasma Concentration (Cmax) of Prostacyclin Receptor Agonist
Description
Cmax is the maximum observed plasma concentration of prostacyclin receptor agonist, during treatment period 2.
Time Frame
Up to 114 days
Title
Treatment Period 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Prostacyclin Receptor Agonist
Description
Tmax is the actual sampling time to reach maximum observed plasma concentration of prostacyclin receptor agonist, during treatment period 2.
Time Frame
Up to 114 days
Title
Treatment Period 2: Area Under the Plasma Concentration-time Curve from time Zero to time t (AUC[0-t]) of Prostacyclin Receptor Agonist
Description
Area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of concentration of prostacyclin receptor agonist, during treatment period 2.
Time Frame
Up to 114 days
Title
Treatment Period 2: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Prostacyclin Receptor Agonist
Description
AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/ lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration of prostacyclin receptor agonist, and lambda (z) is elimination rate constant, during treatment period 2.
Time Frame
Up to 114 days
Title
Treatment Period 2: Area Under the Plasma Concentration-time Curve From Zero to Time 24 Hours (AUC [0-24h]) of Prostacyclin Receptor Agonist
Description
AUC (0-24h) is the area under the plasma concentration-time curve from zero to time 24 hours, during treatment period 2.
Time Frame
Predose up to 24 hours post dose
Title
Treatment Period 2: Area Under the Plasma Concentration-time Curve From Zero to Day 14 (AUC [0-Day 14]) of Prostacyclin Receptor Agonist
Description
AUC (0-Day 14) is the area under the plasma concentration-time curve from zero to Day 14, during treatment period 2.
Time Frame
Up to Day 14
Title
Treatment Period 2: Area Under the Plasma Concentration-time Curve From Zero to Day 28 (AUC [0-Day 28]) of Prostacyclin Receptor Agonist
Description
AUC (0-Day 28) is the area under the plasma concentration-time curve from zero to Day 28, during treatment period 2.
Time Frame
Up to Day 28
Title
Treatment Period 2: Plasma Concentration of Prostacyclin Receptor Agonist at Day 14 (C[Day 14])
Description
C(Day 14) is the plasma concentration of prostacyclin receptor agonist at Day 14, during treatment period 2
Time Frame
Up to Day 14
Title
Treatment Period 2: Plasma Concentration of Prostacyclin Receptor Agonist at Day 28 (C[Day 28])
Description
C(Day 28) is the plasma concentration of prostacyclin receptor agonist at Day 28, during treatment period 2.
Time Frame
Up to Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Otherwise, healthy as deemed by the investigator on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiograms (ECG) performed at Screening and Day -1 of oral treatment period Otherwise, healthy medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, blood coagulation, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator Body mass index (BMI) within the range 18.0 to 32.0 kilograms per meter square (kg/m^2) (inclusive) and body weight not less than 50 kilograms (kg) at screening All female participants must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study intervention Exclusion Criteria: Known allergies, hypersensitivity, anaphylaxis, or intolerance to prostacyclin receptor agonist or drugs of the same class, or any excipient (including poloxamer and polysorbate) of the drug formulation(s) Clinically significant abnormal physical examination, vital signs, or 12-lead ECG (QTc greater than or equal to [>=]450 milliseconds [msec] for men and >=460 msec for women. QT corrected according to Bazett's formula [QTcB]) as assessed by the Investigator at Screening or Day -1 of oral treatment period History of malignancy within 3 years before screening (exceptions are squamous and basal cell carcinomas of the skin Positive serologic testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), active coronavirus disease 2019 (COVID-19) infection A history of repeated (more than once over the last 30 days) fainting due to cardiac cause, collapse, syncope, orthostatic hypotension, or vasovagal reactions
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Contact
Phone
844-434-4210
Email
Participate-In-This-Study@its.jnj.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Actelion Pharmaceuticals Ltd. Clinical Trials
Organizational Affiliation
Actelion
Official's Role
Study Director
Facility Information:
Facility Name
Celerion
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85283
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
http://www.janssen.com/clinical-trials/transparency

Learn more about this trial

A Study of Single and Multiple Doses of Different Formulations of a Prostacyclin Receptor Agonist

We'll reach out to this number within 24 hrs