Clinical Trial Results:
An open-label extension of study AC-066A301 investigating the safety and tolerability of ACT-385781A in patients with pulmonary arterial hypertension (PAH)
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Summary
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EudraCT number |
2010-018320-10 |
Trial protocol |
BE NL ES IT |
Global end of trial date |
15 Jun 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
14 Oct 2017
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First version publication date |
14 Oct 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AC-066A302
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01470144 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
ACTELION Pharmaceuticals Ltd
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Sponsor organisation address |
Gewerbestrasse 16, Allschwil, Switzerland, 4123
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Public contact |
Thomas Pfister, ACTELION Pharmaceuticals Ltd, medinfo_ch@actelion.com
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Scientific contact |
Thomas Pfister, ACTELION Pharmaceuticals Ltd, medinfo_ch@actelion.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Aug 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Jun 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Jun 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess safety and tolerability of Epoprostenol for injection in patients with PAH
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Protection of trial subjects |
Prior to the start of the AC-066A302 study, each study site consulted an Independent
Ethics Committee (IEC) or Institutional Review Board (IRB). Actelion ensured that each IEC/IRB
consulted was adequately constituted to provide assurance of that protection.
The protocol and any written material provided to the subject were reviewed and approved
by the appropriate IEC or IRB before the study was started. Amendments to the protocol
were also reviewed by the appropriate IEC/IRB before their implementation.
The investigator ensured that study AC-066A302 was conducted in full compliance with
the principles of the ‘Declaration of Helsinki’ and its amendments, and with the laws and
regulations of the country in which the clinical research was conducted.
Documentary evidence of adequate Good Clinical Practice (GCP) training of the
investigator was collected. GCP training was provided to investigators, if required. A written commitment to comply with GCP and the study protocol was obtained from the investigator.
The study enrolled patients who had completed AC-066A301 and had not obtained
access to commercially available and reimbursed EFI2 at the time of ending participation
in AC-066A301. Patients participating in AC-066A301 were male or female and
≥ 18 years of age with PAH who had been treated with Flolan® for at least 12 months and
were on a stable dose for at least 3 months prior to enrollment in AC-066A301. The patient population was consistent with the indication approved for Flolan ®. Additional eligibility criteria at enrollment into AC-066A301 were intended to reduce variability due to disease characteristics and co-morbidities. Eligible patients were required to have completed study AC-066A301. Patients for whom continued treatment with EFI2 was no longer considered appropriate were not eligible.
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Background therapy |
Concomitant PAH medications were allowed, except any prostacyclin or prostacyclin analog other than EFI2. Any other concomitant investigational drugs were forbidden. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Jun 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 20
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Netherlands: 4
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Country: Number of subjects enrolled |
Belgium: 5
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Country: Number of subjects enrolled |
Canada: 8
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Worldwide total number of subjects |
41
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EEA total number of subjects |
33
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
38
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Extension study for patients who completed EPITOME-2 (AC-066A301). Patients continued to receive EFI (epoprostenol sodium). In 6 countries (FR, CA, BE, NL, IT, ES) at 8 expert centers for the treatment of patients with pulmonary arterial hypertension. Recruitment started on 15 June 2011 and was completed on 02 February 2012. | ||||||||||||||||
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Pre-assignment
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Screening details |
None | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Treatment | ||||||||||||||||
Arm description |
All patients who received at least one dose of EFI2 | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
epoprostenol sodium
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous drip use
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Dosage and administration details |
EFI2 was supplied in 10-mL glass vials that contained 0.5 or 1.5 mg epoprostenol sodium as a lyophilized powder. EFI2 was reconstituted and further diluted with either sterile water for injection or 0.9% w/v sodium chloride for injection, to obtain the “ready -to-use solution” for injection. This solution was administered by continuous i.v. infusion via a central venous catheter using an ambulatory infusion pump. Infusion sets with an in-line 0.22 micron filter were used. During long-term infusion, the dose of EFI2 was to be adjusted under medical supervision according to therapeutic need and tolerability.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
All patients who received at least one dose of EFI2 | |||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
All treated set
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The All treated set consists of all patients who received at least one dose of study drug in
study AC-066A302 and is identical to the All treated set reported for AC-066A301.
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End points reporting groups
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Reporting group title |
Treatment
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Reporting group description |
All patients who received at least one dose of EFI2 | ||
Subject analysis set title |
All treated set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The All treated set consists of all patients who received at least one dose of study drug in
study AC-066A302 and is identical to the All treated set reported for AC-066A301.
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End point title |
Not applicable [1] | ||||||
End point description |
No primary endpoint was defined. This was an exploratory safety study.
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End point type |
Primary
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End point timeframe |
Not applicable
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This was an exploratory study. No statistical analysis was performed. |
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| Notes [2] - not applicable |
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| No statistical analyses for this end point | |||||||
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End point title |
Treatment-emergent adverse events | ||||||
End point description |
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End point type |
Other pre-specified
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End point timeframe |
Up to 24 hours post treatment
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| No statistical analyses for this end point | |||||||
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End point title |
Exposure duration | ||||||||
End point description |
Duration of exposure to EFI
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End point type |
Other pre-specified
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End point timeframe |
Study start to end of treatment
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From study start to end of treatment plus 1 day.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.0
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Reporting groups
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Reporting group title |
Treatment
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Reporting group description |
Reporting group 1 description | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Nov 2010 |
1. A modification to the formulation of the study drug and resulting changes to its stability, availability and its name were described:
− Changes in study drug excipients were described.
− Instructions for study drug packaging, and preparation, handling and storage of the study drug solution were updated accordingly.
− The drug name was changed to Epoprostenol for injection (EFI).
− An additional dose strength of 0.5 mg was added.
2. The estimated treatment duration (until commercialization of the new formulation) was updated from 4–16 months to 2 years.
3. An increase in the numbers of participating countries and of patients to be enrolled was described, in line with changes made in study AC-066A301.
4. Changes were made in the core patient information and informed consent form.
5. Some editorial changes were made for clarification and to correct typographical errors.
6. The authors of the protocol and the sponsor’s contact details and signatories were changed. |
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15 Jun 2011 |
1. The instructions for the handling and storage of the study drug solution were updated, based on data from an additional in-use stability study that showed that the diluted EFI solution could be stored and administered for longer periods of time than previously described.
2. An increase in the number of patients to be enrolled from 25-30 to 40 patients was described, in line with changes made in study AC-066A301.
3. Changes were made in the core patient information and informed consent form.
4. Some editorial changes were made for clarification and to correct typographical errors.
5. The authors of the protocol and the sponsor’s contact details and signatories were changed. |
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28 Feb 2012 |
1. The instructions for storage and handling of study drug solution were adjusted for consistency with the proposed Summary of Product Characteristics for EFI.
2. Following withdrawal of sitaxentan from the market by its license holder, inclusion criteria and allowed concomitant medications were updated to exclude sitaxentan.
3. The use of an infusion set with an in-line filter was specified in Section 3.3.1 of the protocol, consistent with the proposed Summary of Product Characteristics for EFI. Prior to this Amendment, the use of an in-line filter had been indicated in the list of ancillary supplies (protocol section 3.6.2) only.
4. The planned study duration was revised, with a delay in enrollment anticipated for AC-066A301 and hence AC-066A302.
5. Changes were made in the core patient information and informed consent form.
6. Minor clarifications, including administrative changes and corrections of typographical errors, were made. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/24439982 |
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