Primary objective* To demonstrate the effect of ACT-293987 on time to first morbidity and mortality (MM) event in patients with pulmonary arterial hypertension (PAH).Secondary objective * To evaluate the effect of ACT-293987 on exercise capacity and…
ID
Source
Brief title
Condition
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint
Time to first CEC-confirmed morbidity and mortality (MM) event, up to 7 days
after last study drug intake defined as:
* Death (all-cause mortality)
or
* Hospitalization for worsening of PAH
or
* Worsening of PAH resulting in need for lung transplantation or balloon atrial
septostomy
or
* Initiation of parenteral prostanoid therapy or chronic oxygen therapy due to
worsening of PAH
or
* Disease progression (patients in modified NYHA/WHO functional class II-III at
baseline) confirmed by :
* decrease in 6MWD from Baseline (* 15%, confirmed by two tests on different
days within 2 weeks) and
* worsening of NYHA/WHO functional class
or
* Disease progression (patients in modified NYHA/WHO functional class III-IV at
baseline) confirmed by :
* decrease in 6MWD from Baseline (* 15%, confirmed by 2 tests on different days
within 2 weeks) and
* need for additional PAH specific therapy.
MM events will be adjudicated in a blinded fashion by an independent Critical
Event Committee.
Secondary outcome
Secondary endpoints
* Change from baseline to Week 26 in 6MWD measured at trough
* Absence of worsening from Baseline to Week 26 in modified NYHA/WHO functional
class
* Change from Baseline to Week 26 in Borg dyspnea index
* Time to death up to Study Closure
* Change from Baseline to Week 26 in the sub-scale *Breathlessness* of the
*Symptoms* score in the CAMPHOR questionnaire (at selected centers) (not in
the Netherlands)
* Change from Baseline to Week 26 in the *Symptoms* score of the CAMPHOR
questionnaire (at selected centers) (not in the Netherlands)
Background summary
The medication that is tested in this research is called ACT-293987. It is a
non-prostanoid IP receptor agonist. It is much more specific and more potent in
the activation of the human IP receptor then the currently available IP
receptor agonists.
Patients with PAH have been shown to have deficiency of prostacyclin and of
PGI2 synthase causing an imbalance in prostacyclin (PGI2) and thromboxane A2
(TXA2), it's physiological antagonist. These findings led to the rationale that
targeting the PGI2 pathway with IP receptor agonists could be benificial.
Prostacyclin (epoprostenol) and analogs like treprostinil (intravenous,
subcutaneous and inhaled) and iloprost (inhaled) have already been approved for
PHA. An orally available medicinal product, such as ACT-293987, can provide a
significant contribution in the treatment options for these patients.
Study objective
Primary objective
* To demonstrate the effect of ACT-293987 on time to first morbidity and
mortality (MM) event in patients with pulmonary arterial hypertension (PAH).
Secondary objective
* To evaluate the effect of ACT-293987 on exercise capacity and other secondary
and exploratory efficacy endpoints in patients with PAH.
* To evaluate the safety and tolerability of ACT-293987 in patients with PAH.
Study design
Multicentre, double-blind, randomised, placebo-controlled Phase 3 study.
Intervention
Patients will receive an ACT-293987 tablet or placebo twice daily, in the
morning and in the evening. At weekly intervals (scheduled phone calls or
visits), patients will be up-titrated in increments of 200 µg b.i.d. until
reaching the individual maximum tolerated dose (MTD) within the dose range of
up to maximally 1600 *g b.i.d.
If the investigator identifies a tolerability concern for a patient, the
patient's dose will be reduced to the previous dose level.
At Week 12 (scheduled phone call), the MTD for each patient should be finally
determined and this dose must then be kept unchanged for the last 14 weeks
(from Week 12 on) until the Week 26 (Visit 5) assessment of the primary
endpoint, change in 6MWD.
Randomisation takes place in a 1:1 ratio ACT-293987:placebo.
Study burden and risks
At screening and at baseline there will be a standard physical examination and
a complete laboratory tests. For women of child baring potential a pregnacy
test will be done.
At baseline an ECG will be done. The ECG and complete laboratory tests will be
repeated on week 4, week 8, week 16, month 6, further every 6 months and also
at the end of the study. The risks to subjects associated with participation in
the study are described in E9.
Pulmonary Arterial Hypertension is a serious disease which can not be cured and
might lead to death within a few years. An accurate monitoring with a quick
intervention c.q. medication adjustment is the general guideline within this
group of patients.
Prostacyclin and analogs have already been approved for PHA. However, the
administration routes are not always convenient. Subcutaneous, intravenous and
inhaled administrations have injection site pain and reaction, local pain and
6-9 times daily administration as disadvantage. An orally available medicinal
product, such as ACT-293987, can provide a significant contribution in the
treatment options for these patients.
Gewerbestrasse 16
Allschwil 4123
CH
Gewerbestrasse 16
Allschwil 4123
CH
Listed location countries
Age
Inclusion criteria
- Signed informed consent prior to initiation of any study-mandated procedure.
- Male and female patients aged from 18 years to 75 years inclusive with symptomatic PAH.
- Documented hemodynamic diagnosis of PAH.
Exclusion criteria
- Patients who have received prostacyclin (epoprostenol) or prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) within 1 month before Baseline Visit, or are scheduled to receive any of these compounds during the trial.
- Patients with moderate or severe obstructive lung disease.
- Patients with moderate or severe restrictive lung disease.
- Patients with moderate or severe hepatic impairment (Child-Pugh B and C).
- Patients with documented left ventricular dysfunction.
- Patients with severe renal insufficiency.
- Patients with BMI <18.5 Kg/m2.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-014490-41-NL |
| ClinicalTrials.gov | NCT01106014 |
| CCMO | NL30641.029.10 |