A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension

• Register: ClinicalTrials.gov
• Last refreshed on: 8 April 2024
• Main ID: NCT03492177
• Date of registration: 03/04/2018
• Prospective Registration: Yes
• Primary sponsor: Actelion
• Public title: A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension
• Scientific title: A Prospective, Multicenter, Open Label, Single Arm, Phase 2 Study to Investigate the Safety, Tolerability and Pharmacokinetics of Selexipag in Children With Pulmonary Arterial Hypertension
• Date of first enrolment: July 23, 2018
• Target sample size: 63
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03492177
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Belarus, Belgium, Canada, China, France, Germany, Hungary, Israel, Malaysia, Poland, Romania, Russian Federation, Serbia, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Catherine Boisson
• Affiliation: Actelion

Key inclusion & exclusion criteria

Inclusion Criteria:

- Signed and dated informed consent by the parent(s) or Legally authorized
representative(s) AND assent from developmentally capable children

- Males or females between greater than or equal to (>=) 2 and less than (<) 18 years of
age with weight >= 9 kilograms (kg)

- Pulmonary arterial hypertension (PAH) diagnosis confirmed by documented historical
right heart catheterization (RHC) performed at any time before participant's
enrollment

- PAH with one of the following etiologies:

- idiopathic (iPAH),

- heritable (hPAH),

- associated with congenital heart disease (CHD): PAH with co-incidental CHD;
post-operative PAH (persisting/ recurring/ developing >= 6 months after repair of
CHD)

- Drug or toxin-induced

- PAH associated with HIV

- PAH associated with connective tissue disease

- Word Health Organization functional class (WHO FC) II to III

- Participants treated with an endothelin receptor antagonist (ERA) and/or a
phosphodiesterase type 5 (PDE-5) inhibitor provided that the treatment dose(s) has
been stable for at least 3 months prior to enrollment, or participants who are not
candidates for these therapies

- Females of childbearing potential must have a negative pregnancy test at Screening and
at Enrollment, and must agree to undertake monthly pregnancy tests, and to use a
reliable method of contraception (if sexually active) from screening up to study drug
discontinuation plus 30 days (EOS)

Key Exclusion Criteria:

- Participants with PAH due to portal hypertension, schistosomiasis, pulmonary
veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis

- Participants with PAH associated with Eisenmenger syndrome

- Participants with moderate to large left-to-right shunts

- Participants with cyanotic congenital cardiac lesions such as transposition of the
great arteries, truncus arteriosus, univentricular heart or pulmonary atresia with
ventricular septal defect, as well as Participants with Fontan-palliation

- Participants with pulmonary hypertension due to lung disease

- Previous treatment with Uptravi (selexipag) within 2 weeks prior to enrollment

- Participants having received prostacyclin (epoprostenol) or prostacyclin analogs (that
is, treprostinil, iloprost, beraprost) within 2 months prior to enrollment or are
scheduled to receive any of these compounds during the trial

- Treatment with another investigational drug within 4 weeks prior to enrollment

- History, or current suspicion of intussusception or ileus or gastrointestinal
obstruction as per investigator's judgment

- Uncontrolled thyroid disease as per investigator judgment

- Hemoglobin or hematocrit < 75 percentage (%) of the lower limit of normal range

- Known severe or moderate hepatic impairment

- Clinical signs of hypotension that in the investigator's judgment would preclude
initiation of a PAH-specific therapy

- Participants with severe renal insufficiency

- Known hypersensitivity to the investigational treatment or to any of the excipients of
the drug formulations



Age minimum: 2 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension

Intervention(s)

Drug: selexipag (Uptravi)

Primary Outcome(s)

Area Under the Plasma Concentration-time Curve Over a Dose Interval at Steady State of Selexipag and Its Metabolite ACT-333679 Combined (AUCt, ss, Combined) [Time Frame: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)]

Secondary Outcome(s)

Area Under the Plasma Concentration-Time Curve Over a Dose Interval of ACT-333679 at Steady State (AUCt,ss) [Time Frame: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)]

Maximum Observed Plasma Concentration of Selexipag at Steady State (Cmax,ss) [Time Frame: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)]

Trough Concentration of ACT-333679 at Steady State (Ctrough,ss) [Time Frame: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)]

Area Under the Plasma Concentration-time Curve Over a Dose Interval of Selexipag at Steady State (AUCt,ss) [Time Frame: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)]

Number of Participants With Treatment-emergent Adverse Events (TEAEs) (End of Treatment [EOT] + 3 Days) [Time Frame: EOT+3 days (Up to Week 17)]

Number of Participants With Treatment-emergent Deaths (EOT + 3 Days) [Time Frame: EOT+3 days (Up to Week 17)]

Trough Concentration of Selexipag at Steady State (Ctrough,ss) [Time Frame: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)]

Change From Baseline in Blood Pressure [Time Frame: Up to 7 years]

Change From Baseline Over Time in Body Mass Index (BMI) up to EOT + 3 Days [Time Frame: EOT+ 3 days (Up to Week 17)]

Time to Reach the Maximum Observed Plasma Concentration of ACT-333679 at Steady State (Tmax,ss) [Time Frame: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)]

Change From Baseline in Heart Rate [Time Frame: Up to 7 years]

Change From Baseline in Hematology Parameters (EOT + 3 Days) [Time Frame: EOT+3 days (Up to Week 17)]

Change From Baseline in Chemistry Parameters (EOT + 3 Days) [Time Frame: EOT+3 days (Up to Week 17)]

Change From Baseline Over Time in Height up to EOT+3 Days [Time Frame: EOT+3 days (Up to Week 17)]

Maximum Observed Plasma Concentration of ACT-333679 at Steady State (Cmax,ss) [Time Frame: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)]

Number of Participants With Adverse Events (AEs) Leading to Permanent Discontinuation of Study Drug [Time Frame: Up to 7 years]

Number of Participants With Treatment-emergent Marked Laboratory Abnormalities (EOT + 3 Days) [Time Frame: EOT+3 days (Up to Week 17)]

Number of Participants With Treatment-emergent Electrocardiogram (ECG) Abnormalities (EOT + 3 Days) [Time Frame: EOT+3 days (Up to Week 17)]

Time to Reach the Maximum Observed Plasma Concentration of Selexipag at Steady State (Tmax,ss) [Time Frame: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)]

Change From Baseline in Thyroid Stimulating Hormone (TSH) up to EOT + 3 Days [Time Frame: EOT+3 days (Up to Week 17)]

Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) (EOT + 3 Days) [Time Frame: EOT+3 days (Up to Week 17)]

Change From Baseline in Sexual Maturation (Tanner Stage) up to End of Treatment (EOT + 3 Days) [Time Frame: EOT+ 3 days (Up to Week 17)]

Secondary ID(s)

2018-000145-39

AC-065A203

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/04/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03492177