Clinical Trial Results:
A Phase II trial to assess the efficacy and safety of pasireotide s.c. alone or in
combination with cabergoline in patients with Cushing’s disease
Summary
|
|
EudraCT number |
2013-002170-49 |
Trial protocol |
DE IT ES BE HU GR NL FR |
Global end of trial date |
04 Sep 2019
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
13 Sep 2020
|
First version publication date |
13 Sep 2020
|
Other versions |
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 |
CSOM230B2411
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01915303 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Novartis Pharma Ag
|
||
Sponsor organisation address |
CH-4002, Basel, Switzerland,
|
||
Public contact |
Clinical Disclosure Office, Novartis Pharma aG, 41 613241111, Novartis.email@novartis.com
|
||
Scientific contact |
Clinical Disclosure Office, Novartis Pharma aG, 41 613241111, Novartis.email@novartis.com
|
||
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 |
04 Sep 2019
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
04 Sep 2019
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
To evaluate the overall efficacy of the treatment regimen of pasireotide alone or in combination
with cabergoline in patients with Cushing’s disease (CD)
|
||
Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Mar 2014
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 1
|
||
Country: Number of subjects enrolled |
Spain: 3
|
||
Country: Number of subjects enrolled |
United States: 3
|
||
Country: Number of subjects enrolled |
Colombia: 5
|
||
Country: Number of subjects enrolled |
Turkey: 10
|
||
Country: Number of subjects enrolled |
Belgium: 6
|
||
Country: Number of subjects enrolled |
Brazil: 9
|
||
Country: Number of subjects enrolled |
France: 3
|
||
Country: Number of subjects enrolled |
Greece: 3
|
||
Country: Number of subjects enrolled |
Hungary: 3
|
||
Country: Number of subjects enrolled |
India: 6
|
||
Country: Number of subjects enrolled |
Italy: 2
|
||
Country: Number of subjects enrolled |
Argentina: 2
|
||
Country: Number of subjects enrolled |
Mexico: 6
|
||
Country: Number of subjects enrolled |
Malaysia: 3
|
||
Country: Number of subjects enrolled |
Netherlands: 3
|
||
Worldwide total number of subjects |
68
|
||
EEA total number of subjects |
24
|
||
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) |
64
|
||
From 65 to 84 years |
4
|
||
85 years and over |
0
|
|
|||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||
Screening details |
How many patients were screened | ||||||||||||||||||||
Period 1
|
|||||||||||||||||||||
Period 1 title |
Core Phase
|
||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||
Arms
|
|||||||||||||||||||||
Arm title
|
All patients | ||||||||||||||||||||
Arm description |
Pasireotide montherapy (0.6 mg bid to 0.9 mg bid) was administered until the biochemical control was achieved and if not achieved, a combination was administered: pasireotide (0.9 mg bid) + cabergoline (0.5 QD to 1 mg QD). Patients were able to add cabergoline at anytime during core and extension | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
pasireotide +/- cabergoline
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Solution for injection, Tablet
|
||||||||||||||||||||
Routes of administration |
Oral use, Subcutaneous use
|
||||||||||||||||||||
Dosage and administration details |
pasireotide = 0.3 mg (bid, QD in case of good response), 0.6 mg (bid), and 0.9 mg (bid) and cabergoline = 0.5 mg (QD) or 1.0 mg (QD) In case of lack of tolerability, it can be reduced: 0.5 mg (QOD) or 1.0 mg (QOD)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Period 2
|
|||||||||||||||||||||
Period 2 title |
Extension Phase
|
||||||||||||||||||||
Is this the baseline period? |
No | ||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||
Arms
|
|||||||||||||||||||||
Arm title
|
All patients | ||||||||||||||||||||
Arm description |
Pasireotide montherapy (0.6 mg bid to 0.9 mg bid) was administered until the biochemical control was achieved and if not achieved, a combination was administered: pasireotide (0.9 mg bid) + cabergoline (0.5 QD to 1 mg QD). Patients were able to add cabergoline at anytime during core and extension | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
pasireotide +/- cabergoline
|
||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Solution for injection, Tablet
|
||||||||||||||||||||
Routes of administration |
Subcutaneous use, Oral use
|
||||||||||||||||||||
Dosage and administration details |
pasireotide = 0.3 mg (bid, QD in case of good response), 0.6 mg (bid), and 0.9 mg (bid) and cabergoline = 0.5 mg (QD) or 1.0 mg (QD) In case of lack of tolerability, it can be reduced: 0.5 mg (QOD) or 1.0 mg (QOD)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: All patients did not enter the extension |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
All patients
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Pasireotide montherapy (0.6 mg bid to 0.9 mg bid) was administered until the biochemical control was achieved and if not achieved, a combination was administered: pasireotide (0.9 mg bid) + cabergoline (0.5 QD to 1 mg QD). Patients were able to add cabergoline at anytime during core and extension | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
All patients
|
||
Reporting group description |
Pasireotide montherapy (0.6 mg bid to 0.9 mg bid) was administered until the biochemical control was achieved and if not achieved, a combination was administered: pasireotide (0.9 mg bid) + cabergoline (0.5 QD to 1 mg QD). Patients were able to add cabergoline at anytime during core and extension | ||
Reporting group title |
All patients
|
||
Reporting group description |
Pasireotide montherapy (0.6 mg bid to 0.9 mg bid) was administered until the biochemical control was achieved and if not achieved, a combination was administered: pasireotide (0.9 mg bid) + cabergoline (0.5 QD to 1 mg QD). Patients were able to add cabergoline at anytime during core and extension |
|
|||||||||
End point title |
Percentage of responders with mean urinary free cortisol (mUFC) ≤ 1.0xULN collected or imputed at week 35 [1] | ||||||||
End point description |
Participants who attained mUFC ≤ 1.0 x ULN (upper limit of normal) with pasireotide alone or in combination with cabergoline. The 24h-UFC concentration results from three samples, collected during the screening period, were averaged to obtain the Baseline urinary free cortisol level. mean 24h-UFC was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit. Imputation: subjects who completed the end of treatment visit at Week 35, but had missing evaluation of mean urinary free cortisol (mUFC). The last available mUFC assessment at or after previous visit (week) before last week was carried forward as the last week mUFC assessment.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Baseline up to week 35
|
||||||||
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: Not analyzed |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Mean urinary free cortisol (mUFC) at scheduled visits | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Percentage of responders with mean Urinary Free Cortisol (mUFC) ≤ 1.0xULN | ||||||||||||||||||||||||||||||||
End point description |
Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline up to week 235
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||
End point title |
Percentage of participants who attain mUFC ≤ 1.0 x ULN or have at least 50% reduction from baseline in mUFC | ||||||||||||||||||||||||||||||||
End point description |
Actual mean value of mUFC at each scheduled visit was determined from two 24-hour urine collections collected on two consecutive days that occurred before the visit when UFC was measured.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Baseline up to week 235
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Duration (weeks) of controlled or partially controlled response | ||||||||||||
End point description |
Duration of controlled or partially controlled response is defined as the period starting from the date of patient's first normalization (mUFC ≤ 1.0 x ULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN and the reduction from baseline falls to less than 50% from the first time
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
from the date patient's first normalization (mUFC ≤ 1.0xULN) or at least 50% reduction from baseline up to the date when the patient's mUFC > 1.0 x ULN
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Plasma adrenocorticotropic hormone (ACTH) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
A pre-dose blood draw for plasma ACTH sampling was taken at visits. Samples were analyzed by a central laboratory.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Serum cortisol levels | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
A pre-dose blood draw for an 8 am fasting serum cortisol measurement will be taken at visits. Samples were analyzed by a central laboratory.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sitting systolic blood pressure at week 35 | ||||||||||||
End point description |
The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 35
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Sitting diastolic blood pressure at week 35 | ||||||||||||
End point description |
The mean arterial blood pressure determinations were obtained in the sitting position. Three measurements were taken with 5 minute intervals and the mean was used for study specific procedures
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 35
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Body weight at baseline and week 35 | ||||||||||||
End point description |
Weight was was one of the measures of clinical symptoms of CD
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 35
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Body mass index at week 35 | ||||||||||||
End point description |
Body mass index was one of the measurements of clinical symptoms of CD. Body mass index=weight in kg divided by the square of the body height (in meters)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 35
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Waist circumference at week 35 | ||||||||||||
End point description |
Waist circumference was one of the measurements of clinical signs of CD
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 35
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
LDL, HDL and total cholesterol at week 35 | ||||||||||||||||||||
End point description |
LDL=Low density lipoprotein, HDL=high density llipoprotein and total protein were analyzed by a central laboratory
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Baseline and week 35
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Mean scores for Cushing QoL standardized score at week 17 and 35 | ||||||||||||||
End point description |
Patients who completed nine or more items for the 12-item Cushing’s syndrome QoL questionaire were considered evaluable for that assessment. Raw scores were obtained for the 12 items using the following scoring: 1) always or very much, 2) often or quite a bit, 3) sometimes or somewhat, 4) rarely or very little, 5) never or not at all. Then the standardized score, Y, was calculated for each patient as follows: Y = 100* (X – n) / n*5 – n*1) = 100 * (X – n) / 4*n where X denoted the raw score and n the number of questions answered by the patient. The higher the score, the better the QoL. The best possible standardized score was 100 and the worst possible standardized score was 0
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline and week 17 and 35
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Mean scores of SF-12v2 domain scores at week 17 and 35 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
SF-12v2 General Health Survey is a general patient reported outcome instrument over time. It is scored to provide eight health domain scores (Bodily Pain (BP), General Health (GH), Physical Functioning (PF), Role-Physical (RP), Social Functioning (SF), Role-Emotional (RE), Vitality (VT) and Mental Health (MH)). These eight domain scores can be combined to form two summary scores reflecting overall physical and mental health: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The analyses reported here focus on PCS and MCS scores. The domain scores use a norm-based score, which standardizes the scores with respect to the mean and standard deviation of a nationally representative sample of United States (US) adults. These are the scores on the original scale which have not been transformed in any way. The possible range of scores is 0 to 100, with higher scores representing better outcomes.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, week 17 and 35
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with improvement in clinical symptom of hypercortisolism from baseline - Facial rubor | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora,
supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with improvement in clinical symptom of hypercortisolism from baseline - Hirsutism | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora,
supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with improvement in clinical symptom of hypercortisolism from baseline - Striae | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora,
supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with improvement in clinical symptom of hypercortisolism from baseline - Supraclavicular fat pad | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora,
supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with improvement in clinical symptom of hypercortisolism from baseline - Dorsal fat pad | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Clinical symptoms include: facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up were taken to assess facial plethora,
supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position were taken to assess striae, and hirsutism. The photographs were assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 16 weeks during extension
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with shift from mild to severe in clinical signs of hypercortisolism | ||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Facial rubor, hirsutism, striae, and supraclavicular and dorsal fat pad. Two photographs, one frontal and one lateral from the shoulders up will be taken to assess facial plethora,
supraclavicular and dorsal fat pads. Two photographs, frontal and dorsal of the trunk with patient in standing position will be taken to assess striae, and hirsutism. The photographs must be assessed by a qualified physician at the site. Improvement=decrease in severity of symptom since baseline
|
||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Baseline, weeks 2, 4, every 4 or 5 weeks during core, every 8 weeks during extension
|
||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Number of patients with shift from standing easily to not being able to stand | ||||||||||
End point description |
To test proximal muscle strength patients should be placed in a low seated position (for instance on an examination room stool). They should be asked to extend the arms in front of them. From this seated position patients will be asked to stand up. Patients will be evaluated
using the following scale:
3. – completely unable to stand
2. – able to stand only by using arms as assistance
1. – able to stand after several efforts without using arms as assistance
0. – able to stand easily with arms extended
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Baseline up to week 267
|
||||||||||
|
|||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Timeframe for AE
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
AE additional description
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
All Patients core@and extension phase
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All Patients core@and extension phase | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
||
19 Mar 2014 |
● To add a criterion to exclude pregnant or nursing (lactating) women;
● It was clarified that Dostinex (a generic form of cabergoline) would be used
for the trial in available participating countries |
||
24 Jul 2015 |
●To combine group 1 (pasireotide naïve subjects) and group 2 (subjects
currently treated with maximal tolerated doses of pasireotide monotherapy) into
a single cohort of subjects;
● To reduce the target number of enrolled subjects (reduced from 128 to 64);
● The duration of screening period was increased from 21 days to 28 days;
● To change the lowest dose of pasireotide allowed for the trial (previous dose
0.3 mg bid; new dose: 0.3 mg QD).
● The PK analysis was not performed as a result of combining group 1 and
group 2 into one single group. |
||
25 Jul 2016 |
At the time of this protocol amendment, pasireotide was not yet approved for commercial use and/or reimbursed in several participating countries. In order to continue to provide access to treatment for subjects in these countries and to collect longer-term safety and efficacy data, the maximum duration of the extension phase of the study was extended by two further years. The new enddate for the extension phase is 31-Dec-2017; Addition of one section “Adverse events of special interest” |
||
12 Jul 2017 |
At the time of this protocol amendment, pasireotide was not yet approved for commercial use and/or reimbursed in several participating countries. In order to continue to provide access to treatment for subjects in these countries and to collect longer-term safety and efficacy data, the maximum duration of the extension phase of the study was extended by two further years. The new end date for the extension phase is 31-Dec-2019. |
||
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 |