Clinical Trial Results:
An open-label extension study of the long-term safety, tolerability and efficacy of ambrisentan in subjects with inoperable chronic thromboembolic pulmonary hypertension (CTEPH)
|
Summary
|
|
EudraCT number |
2012-001642-17 |
Trial protocol |
ES AT DE GB CZ NL IT |
Global end of trial date |
18 Nov 2015
|
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
03 Aug 2017
|
First version publication date |
30 Jul 2016
|
Other versions |
v1 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
AMB116457
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
GlaxoSmithKline
|
||
Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
|
||
Public contact |
GSK Response Center, GlaxoSmithKline, 1-866 4357343,
|
||
Scientific contact |
GSK Response Center, GlaxoSmithKline, 1-866 4357343,
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
07 Apr 2016
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
18 Nov 2015
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective is the long-term safety and tolerability of ambrisentan in the CTEPH population (see Safety).
- Safety assessments:
- Adverse Events;
- Serious Adverse Events;
- Clinical laboratory parameters (including liver safety and haematological parameters);
- Physical examination (including jugular venous pressure, liver size, peripheral oedema, ascites and signs of deep vein thrombosis);
- Vital Signs (including body mass index at the entry visit only);
The time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to tolerability issues (e.g. adverse events).
|
||
Protection of trial subjects |
The Independent Data Monitoring Committee (IDMC) recommended that the Sponsor stop the study at any time if they consider that the potential risks outweigh the potential benefits (based on review of safety [adverse experiences] data every three months).
A subject may also be discontinued from Investigational Product, or from the study, for the following reasons:
• Liver chemistry values exceeding the threshold criteria (as outlined in the protocol);
• Adverse event which in the opinion of the investigator requires withdrawal;
• Pregnancy;
• Consent withdrawn;
• Lost to follow-up;
• Protocol violation;
• Termination of study by sponsor;
• Investigator’s discretion (document reason in eCRF).
Subjects discontinuing investigation product are encouraged to stay in the study at their and the investigators discretion.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Jan 2014
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Japan: 3
|
||
Country: Number of subjects enrolled |
China: 3
|
||
Country: Number of subjects enrolled |
Mexico: 2
|
||
Country: Number of subjects enrolled |
Russian Federation: 1
|
||
Country: Number of subjects enrolled |
Netherlands: 1
|
||
Country: Number of subjects enrolled |
Spain: 4
|
||
Country: Number of subjects enrolled |
United Kingdom: 1
|
||
Country: Number of subjects enrolled |
Czech Republic: 1
|
||
Country: Number of subjects enrolled |
Germany: 3
|
||
Worldwide total number of subjects |
19
|
||
EEA total number of subjects |
10
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
12
|
||
From 65 to 84 years |
7
|
||
85 years and over |
0
|
||
|
||||||||||||||||||||||
|
Recruitment
|
||||||||||||||||||||||
Recruitment details |
This was an open label, long-term extension study to the double-blind, placebo-controlled study AMB115811 (NCT01884675). Only those participants (par.) in study AMB115811 were eligible for enrollment in this study. The planned duration was a minimum of 18 months, but the study was terminated due to futility of enrollment in study AMB115811. | |||||||||||||||||||||
|
Pre-assignment
|
||||||||||||||||||||||
Screening details |
Out of the 33 participants randomized (16 participants in the Placebo arm and 17 in the Ambrisentan arm) in study AMB115811, a total of 19 participants were enrolled in this extension study. | |||||||||||||||||||||
|
Period 1
|
||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
|||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||
|
Arms
|
||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||
|
Arm title
|
Previous Placebo | |||||||||||||||||||||
Arm description |
Participants received placebo tablet once daily (OD) for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants received ambrisentan 5 milligrams (mg) tablet OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
5 mg or 10 mg of Ambrisentan
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
5 mg or 10 mg tablet of Ambrisentan administered orally once daily
|
|||||||||||||||||||||
|
Arm title
|
Previous Ambrisentan | |||||||||||||||||||||
Arm description |
Participants received ambrisentan 5 mg tablet OD for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants continued to receive ambrisentan 5 mg OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
5 mg or 10 mg of Ambrisentan
|
|||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||
Dosage and administration details |
5 mg or 10 mg tablet of Ambrisentan administered orally once daily
|
|||||||||||||||||||||
|
||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Previous Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received placebo tablet once daily (OD) for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants received ambrisentan 5 milligrams (mg) tablet OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Previous Ambrisentan
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received ambrisentan 5 mg tablet OD for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants continued to receive ambrisentan 5 mg OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Previous Placebo
|
||
Reporting group description |
Participants received placebo tablet once daily (OD) for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants received ambrisentan 5 milligrams (mg) tablet OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD. | ||
Reporting group title |
Previous Ambrisentan
|
||
Reporting group description |
Participants received ambrisentan 5 mg tablet OD for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants continued to receive ambrisentan 5 mg OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD. | ||
Subject analysis set title |
Previous Placebo
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants received placebo tablet once daily (OD) for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants received ambrisentan 5 milligrams (mg) tablet OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD.
|
||
Subject analysis set title |
Previous Ambrisentan
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Participants received ambrisentan 5 mg tablet OD for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants continued to receive ambrisentan 5 mg OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD.
|
||
|
||||||||||||||||
End point title |
Number of participants with any adverse event (AE) or serious adverse event (SAE) [1] | |||||||||||||||
End point description |
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect. Refer to the general AE/SAE module for a list of AEs and SAEs. Participant's final visit in Study AMB115811 was used as the entry visit of this open-label extension study. Safety (Extension) Population: all participants who enrolled and took at least one dose of study treatment during the extension study.
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
From Entry Visit of the extension study up to approximately 16 months
|
|||||||||||||||
| 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: There are no statistical data to report. |
||||||||||||||||
|
||||||||||||||||
| Notes [2] - Safety (Extension) Population [3] - Safety (Extension) Population |
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in basophils, eosinophils, lymphocytes, monocytes, total neutrophils (Absolute Neutrophil Count [ANC]), platelet count, and white blood cell (WBC) count at the indicated time points [4] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC), platelet count, and WBC count are summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in Study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Instances where 99999 has been mentioned indicate that data was not available or participants were not analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [4] - 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: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [5] - Safety (Extension) Population [6] - Safety (Extension) Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points [7] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in hemoglobin and MCHC is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in Study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Instances where 99999 has been mentioned indicate that data was not available or participants were not analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [7] - 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: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [8] - Safety (Extension) Population [9] - Safety (Extension) Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in hematocrit at the indicated time points [10] | ||||||||||||||||||||||||||||||||||||
End point description |
Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in hematocrit is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Instances where 99999 has been mentioned indicate that data was not available or participants were not analyzed.
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
|
||||||||||||||||||||||||||||||||||||
| Notes [10] - 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: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| Notes [11] - Safety (Extension) Population [12] - Safety (Extension) Population |
|||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in mean corpuscle volume at the indicated time points [13] | ||||||||||||||||||||||||||||||||||||
End point description |
Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in mean corpuscle volume is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Instances where 99999 has been mentioned indicate that data was not available or participants were not analyzed.
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
|
||||||||||||||||||||||||||||||||||||
| Notes [13] - 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: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| Notes [14] - Safety (Extension) Population [15] - Safety (Extension) Population |
|||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in red blood cell count and reticulocytes at the indicated time points [16] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in red blood cell count and reticulocytes is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Instances where 99999 has been mentioned indicate that data was not available or par. were not analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [16] - 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: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [17] - Safety (Extension) Population [18] - Safety (Extension) Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Number of participants with clinical chemistry parameters of potential clinical concern at any time post entry visit [19] | |||||||||||||||||||||
End point description |
Blood samples were collected post Entry visit of the extension study and up to end of study for evaluation of the clinical chemistry parameters of alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GGT), and total bilirubin. The clinical chemistry parameters of potential clinical concern high were defined as follows: ALT, AST, GGT >=3 times upper limit of normal (ULN); total bilirubin >=2 times ULN. Participants with both normal and high values were counted once under their worst case (high). Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study.
|
|||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||
End point timeframe |
Post entry visit of the extension study and up to End of Study (assessed up to approximately 16 months)
|
|||||||||||||||||||||
| Notes [19] - 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: There are no statistical data to report. |
||||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [20] - Safety (Extension) Population [21] - Safety (Extension) Population |
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||
End point title |
Number of participants with creatinine values of potential clinical concern at any time post entry visit [22] | ||||||||||||
End point description |
Blood samples were collected at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study plus any unscheduled lab tests for creatinine. A creatinine value of potential clinical concern high was defined as >=176.8 micromoles per Liter. Participants with both normal and high values were counted once under their worst case (high). Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study plus any unscheduled lab tests (assessed up to approximately 16 months)
|
||||||||||||
| Notes [22] - 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: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
| Notes [23] - Safety (Extension) Population [24] - Safety (Extension) Population |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) assessed at the indicated time points [25] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Vital signs including SBP and DBP were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in SBP and DBP is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Instances where 99999 has been mentioned indicate that data was not available or par. were not analyzed.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [25] - 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: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [26] - Safety (Extension) Population [27] - Safety (Extension) Population |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in heart rate at the indicated time points [28] | ||||||||||||||||||||||||||||||||||||
End point description |
Vital signs including heart rate were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in heart rate is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Instances where 99999 has been mentioned indicate that data was not available or par. were not analyzed.
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
|
||||||||||||||||||||||||||||||||||||
| Notes [28] - 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: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| Notes [29] - Safety (Extension) Population [30] - Safety (Extension) Population |
|||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in weight at the indicated time points [31] | ||||||||||||||||||||||||||||||||||||
End point description |
Weight was measured at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and at end of study. Change from study AMB115811 Baseline in weight is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Instances where 99999 has been mentioned indicate that data was not available or par. were not analyzed.
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
|
||||||||||||||||||||||||||||||||||||
| Notes [31] - 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: There are no statistical data to report. |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
| Notes [32] - Safety (Extension) Population [33] - Safety (Extension) Population |
|||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Time to first change in dose of open-label ambrisentan due to tolerability issues in any participant [34] | ||||||||||||
End point description |
The time to change in dose of ambrisentan or other targeted PAH (pulmonary arterial hypertension) therapeutic agents (prostanoids, PDE-5 inhibitors) due to tolerability issues (e.g. adverse events). Dosing data were collected, but after the study was terminated, not all endpoints listed in the protocol were analyzed, including time to first change in dose of open-label ambrisentan. This decision was documented in the reporting and analysis plan prior to database lock.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
From the Entry visit of the extension study up to approximately 16 months
|
||||||||||||
| Notes [34] - 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: There are no statistical data to report. |
|||||||||||||
|
|||||||||||||
| Notes [35] - This data was not analyzed. [36] - This data was not analyzed. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in the 6 minutes walking distance (6MWD) at the indicated time points | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The 6-minute walk test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. 6MWD was measured by a 6-minute walk test. This test measures the distance that a par. can walk in a period of 6 minutes. AMB115811 Baseline was the Week 0 value in that study. Change from study AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Par.'s final visit in study AMB115811 was used as the entry visit of this extension study. For the Extension study, the visit schedule (Months 1, 3, 6, 9, 12 and 15) was mapped to the visit schedule (Months 5, 7, 10, 13, 16 and 19) for continuity with study AMB115811. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Intent-to-treat (ITT) Population: all par. who were randomized and took at least one dose of study medication in the double-blind phase (placebo or ambrisentan).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During Study AMB115811: Months 0 (Baseline), 1, 2, 3, 4, Early Withdrawal (EW); During Extension Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [37] - ITT Population [38] - ITT Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline (BL) in World Health Organization (WHO) functional class (FC) at the indicated time points | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
WHO FC indicates severity of pulmonary arterial hypertension (PAH) and is an adaptation of the New York Heart Association classification, assessed by the investigator. There are 4 grades for WHO FC based on severity of symptoms (Class I = none, Class IV = most severe). Grades mapped to numeric scale 1-4 (i.e. Class IV = 4). WHO FC system links symptoms with activity limitations, allowing clinicians to predict disease progression and prognosis. AMB115811 BL is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 BL was calculated as the value at the indicated visit minus the BL value (positive change = worsening). Par.'s final visit in AMB115811 was used as entry visit of this ext study. For Ext study, the visit schedule (M1,3,6,9,12 and 15) was mapped to the visit schedule (M5,7,10,13,16 and 19) for continuity with study AMB115811. Only par. available at the specified TP were analyzed (represented by n=X,X in the category title).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During Study AMB115811: Months 0 (Baseline), 1, 2, 3, 4, Early Withdrawal; During Extension Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [39] - ITT Population [40] - ITT Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from study AMB115811 Baseline in Borg CR10 Scale (BCR10S) immediately following exercise at the indicated time points | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
BCR10S score was collected immediately following completion of the 6-minute walk test. Scores range from 0 to 10 (0=nothing at all, 10=extremely strong). If par.'s perception or feeling was stronger than "10", that is “extremely strong”, “Maximal” – a larger number could be used, for example 12 or still higher, that is “Absolute maximum”). AMB115811 BL data was calculated as average of 2 BCR10S values obtained following the 2 6MWD tests used in determining the BL 6MWD in that study. If only 1 measurement was available, it was used. Change from AMB115811 BL was calculated as the value at the indicated visit minus the BL value. Par.'s final visit in AMB115811 was used as the entry visit of extension study. For the Extension study, the visit schedule (Months 1, 3, 6, 9, 12 and 15) mapped to the visit schedule (Months 5, 7, 10, 13, 16 and 19) for continuity with AMB115811. Only those par. available at the specified time points were analyzed (represented by n=X,X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During Study AMB115811: Months 0 (Baseline), 1, 2, 3, 4, Early Withdrawal; During Extension Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [41] - ITT Population [42] - ITT Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Number of participants with clinical worsening of chronic thromboembolic pulmonary hypertension (CTEPH) | ||||||||||||
End point description |
Time to clinical worsening of CTEPH was defined as the time from randomization in Study AMB115811 to the first occurrence of any of the following events: death (all cause), lung transplantation, hospitalization for CTEPH deterioration, atrial septostomy, addition of parenteral prostanoids, appearance of two or more CTEPH worsening events. Worsening events included: >=20% of decrease in 6MWD; >=1 increase of WHO Functional Classes; worsening right ventricular failure; rapidly progressing cardiogenic, hepatic, or renal failure; refractory systolic hypotension (SBP <85 mmHg).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From randomization up to End of Study for the extension study (assessed up to approximately 20 months)
|
||||||||||||
|
|||||||||||||
| Notes [43] - ITT Population [44] - ITT Population |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Change from study AMB115811 Baseline in Quality of Life as measured by Short Form 36 Health Survey (SF-36) | ||||||||||||
End point description |
The SF-36 version 2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health as well as 2 summary measures (Physical Health and Mental Health). Each domain is scored from 0 (poorer health) to 100 (better health). Baseline of study AMB115811 was to be used. Change from study AMB115811 Baseline was to be calculated as the value at the indicated visit minus the Baseline value. The SF-36 data were collected, but after the study was terminated, not all endpoints listed in the protocol were analyzed, including the SF-36. This decision was documented in the reporting and analysis plan prior to database lock.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline from study AMB115811 up to End of Study for the extension study (assessed up to approximately 20 months from Baseline)
|
||||||||||||
|
|||||||||||||
| Notes [45] - Health outcomes data collected in this study were excluded from analysis. [46] - Health outcomes data collected in this study were excluded from analysis. |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percent change from study AMB115811 Baseline in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The ratio to Baseline in NT-proBNP was calculated as the ratio of the value at the specified time-point to the AMB115811 Baseline value and was expressed as a percent change from AMB115811 Baseline. This was done by taking the mean change on the log scale, exponentiating, subtracting 1 and multiplying by 100. Standard deviation (SD) of the logged values (log[SD]) have been presented. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. For the Extension study, the visit schedule (Months 1, 3, 6, 9, 12 and 15) was mapped to the visit schedule (Months 5, 7, 10, 13, 16 and 19) for continuity with study AMB115811. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During Study AMB115811: Months 0 (Baseline), 1, 2, 3, 4, Early Withdrawal; During Extension Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months from Baseline)
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [47] - ITT Population [48] - ITT Population |
|||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Start of Ambrisentan Treatment in 6 minutes walking distance at the indicated time points | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The 6 minute walk distance data in a previous outcome measure were also analyzed as change from start of ambrisentan treatment. As participants started to receive ambrisentan treatment in two studies, two different time points for start of ambrisentan treatment were used for this analysis. For participants who received ambrisentan treatment in Study AMB115811, the Baseline for that study was used. For participants who received placebo in Study AMB115811, entry visit of the Extension study was defined as Baseline. Change from start of ambrisentan was calculated as the value at the indicated visit minus the start of ambrisentan value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category title). Instances where 99999 has been mentioned indicate that data was not available or par. were not analyzed.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [49] - ITT Population. Placebo arm: includes par. who received ambrisentan treatment during extension study [50] - ITT Population |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Start of Ambrisentan Treatment in World Health Organization (WHO) functional class (FC) at the indicated time points | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The WHO functional class data in a previous outcome measure were also analyzed as change from start of ambrisentan treatment. As participants started to receive ambrisentan treatment in two studies, two different time points for start of ambrisentan treatment were used for this analysis. For participants who received ambrisentan treatment in Study AMB115811, the Baseline for that study was used. For participants who received placebo in Study AMB115811, entry visit of the Extension study was defined as Baseline. Change from start of ambrisentan was calculated as the value at the indicated visit minus the start of ambrisentan value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category title). Instances where 99999 has been mentioned indicate that data was not available or par. were not analyzed.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [51] - ITT Population. Placebo arm: includes par. who received ambrisentan treatment during extension study [52] - ITT Population |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Change from Start of Ambrisentan Treatment in Borg CR10 Scale (BCR10S) immediately following exercise at the indicated time points | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The BCR10S data in a previous outcome measure were also analyzed as change from start of ambrisentan treatment. BCR10S score, a rating of perceived exertion, ranges from 0 to 10 (0=nothing at all, 10 extremely strong). If par.’s perception or feeling was stronger than “10”, a larger number could be used. As participants started to receive ambrisentan treatment in two studies, two different time points for start of ambrisentan treatment were used for this analysis. For participants who received ambrisentan treatment in Study AMB115811, the Baseline for that study was used. For participants who received placebo in Study AMB115811, entry visit of the Extension study was defined as Baseline. Change from start of ambrisentan was calculated as the value at the indicated visit minus the start of ambrisentan value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category title).
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [53] - ITT Population. Placebo arm: includes par. who received ambrisentan treatment during extension study [54] - ITT Population |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percent change from Start of Ambrisentan Treatment in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The NT-proBNP data in a previous outcome measure were also analyzed as change from start of ambrisentan treatment. The ratio to start of ambrisentan in NT-proBNP was calculated as the ratio of the value at the specified time-point to the start of ambrisentan value and was expressed as a percent change from start of ambrisentan. This was done by taking the mean change on the log scale, exponentiating, subtracting 1 and multiplying by 100. Standard deviation (SD) of the logged values (log[SD]) have been presented. As par. started to receive ambrisentan treatment in 2 studies, 2 different time points for start of ambrisentan treatment were used for this analysis. For par. who received ambrisentan treatment in study AMB115811, the Baseline for that study was used. For par. who received placebo in Study AMB115811, entry visit of the Extension study was defined as Baseline. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category title).
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [55] - ITT Population. Placebo arm: includes par. who received ambrisentan treatment during extension study [56] - ITT Population |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Time to first change in dose of open-label ambrisentan due to deterioration of clinical conditions in any participant | ||||||||||||
End point description |
The time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition. Dosing data were collected, but after the study was terminated, not all endpoints listed in the protocol were analyzed, including time to first change in dose of open-label ambrisentan. This decision was documented in the reporting and analysis plan prior to database lock.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months)
|
||||||||||||
|
|||||||||||||
| Notes [57] - Data were not analyzed [58] - Data were not analyzed |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time to first addition of another targeted PAH therapeutic agent due to deterioration of clinical condition or lack of beneficial effect with previous therapy in any participant | ||||||||||||
End point description |
The time to addition of another targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to the following reasons: Deterioration of clinical condition; Lack of beneficial effect with previous therapy (not reaching set treatment goals). PAH therapies were collected, but after the study was terminated, not all endpoints listed in the protocol were analyzed, including time to first addition of another targeted PAH therapeutic agent. This decision was documented in the reporting and analysis plan prior to database lock.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months)
|
||||||||||||
|
|||||||||||||
| Notes [59] - Data were not analyzed [60] - Data were not analyzed |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Treatment-emergent adverse events (TEAEs) will include AEs up to 30 days after their last dose, assessed up to approximately 16 months.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
TEAEs are reported for the Safety (Extension) Population. TEAEs are: a) new events that started during the extension study. For par. withdrawn from the study, TEAEs included AEs up to 30 days after last dose b) ongoing AEs that started before the extension study but were either not reported in study AMB115811 or worsened during the extension study.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Previous Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received placebo tablet once daily (OD) for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants received ambrisentan 5 milligrams (mg) tablet OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Previous Ambrisentan
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received ambrisentan 5 mg tablet OD for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants continued to receive ambrisentan 5 mg OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Mar 2013 |
Update to maximum study sample size following changes to the Double-Blind study (AMB115811)
Correction to the IP storage conditions to change from 15-30ºC to up to 30 ºC.
Revision of pregnancy follow-up information to include partners of male subjects in the study and to be consistent with the AMB115811 study
Correct to the description of several efficacy assessments and timepoints to remove the requirement to perform efficacy tests 30 days after discontinuation of IP (safety only is required for this follow-up)
|
||
03 Jul 2013 |
Clarification on the study design: subject’s study participation duration
Clarifications on inclusion criteria:
-in case of prematurely withdrawal from study AMB115811 for whatever reason, the investigator to decide whether or not the subject received the IP.
-addition of some general inclusion criteria on reliable methods of contraception, non participation to another study and signature of the approved consent form.
Clarification on the treatment given after the end of the study
Change in the visit window of month 1 and monthly visits (+/- 7 days)
Vital signs, clarification on blood pressure measurements
Clarification on the study medication storage temperatures
|
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
