Study to Assess the Efficacy and Safety of Repeated Administration of BIM 23A760 in Patients With Acromegaly (TULIPIA)

This study has been terminated.
(Preliminary data from this study does not support expected inhibition of GH and IGF-1)
Sponsor:
Information provided by (Responsible Party):
Ipsen
ClinicalTrials.gov Identifier:
NCT00994214
First received: October 13, 2009
Last updated: January 7, 2016
Last verified: November 2015
Results First Received: October 14, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Acromegaly
Intervention: Drug: BIM 23A760

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This was a multicentre study conducted at 36 investigational sites in 16 countries: Czech Republic, Lithuania, Poland, Romania, Ukraine, Latvia, USA, United Kingdom (UK), Italy, Mexico, Brazil, France, Belgium, Netherlands, Germany and Sweden.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screened subjects were 109 and screen failures were 33. Subjects randomised and treated in part A were 76. Subjects completed part A were 21 and subjects entered Part B were 12, excluding 9 subjects, who chose not to continue in part B. No subjects completed the study.

Reporting Groups
  Description
Arm A: BIM 23A760 1 mg BIM 23A760 1 mg subcutaneous 24 weekly injections.
Arm B: BIM 23A760 2 mg BIM 23A760 2 mg subcutaneous 24 weekly injections.
Arm C: BIM 23A760 4 mg BIM 23A760 4 mg subcutaneous 24 weekly injections.
Arm D: BIM 23A760 6 mg BIM 23A760 6 mg subcutaneous 24 weekly injections.

Participant Flow for 2 periods

Period 1:   ITT (Intention-to-Treat) - Part A
    Arm A: BIM 23A760 1 mg     Arm B: BIM 23A760 2 mg     Arm C: BIM 23A760 4 mg     Arm D: BIM 23A760 6 mg  
STARTED     19     19     18     20  
COMPLETED     5     6     5     5  
NOT COMPLETED     14     13     13     15  
Adverse Event                 0                 1                 0                 0  
Withdrawal by Subject                 0                 0                 0                 1  
Lost to Follow-up                 1                 0                 0                 0  
Withdrawn - Study termination by sponsor                 13                 12                 13                 14  

Period 2:   ITT (Intention-to-Treat) - Part B
    Arm A: BIM 23A760 1 mg     Arm B: BIM 23A760 2 mg     Arm C: BIM 23A760 4 mg     Arm D: BIM 23A760 6 mg  
STARTED     4 [1]   3 [2]   2 [3]   3 [4]
Received Maximum Dose of 1mg     0     0     0     0  
Received Maximum Dose of 2mg     3     0     0     0  
Received Maximum Dose of 4mg     1     3     0     0  
Received Maximum Dose of 6mg     0     0     2     3  
COMPLETED     0     0     0     0  
NOT COMPLETED     4     3     2     3  
Withdrawal by Subject                 0                 0                 0                 1  
Withdrawn - Study termination by sponsor                 4                 3                 2                 2  
[1] 1 subject did not enter Part B Arm A
[2] 3 subjects did not enter Part B Arm B
[3] 3 subjects did not enter Part B Arm C
[4] 2 subjects did not enter Part B Arm D



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm A: BIM 23A760 1 mg BIM 23A760 1 mg subcutaneous 24 weekly injections.
Arm B: BIM 23A760 2 mg BIM 23A760 2 mg subcutaneous 24 weekly injections.
Arm C: BIM 23A760 4 mg BIM 23A760 4 mg subcutaneous 24 weekly injections.
Arm D: BIM 23A760 6 mg BIM 23A760 6 mg subcutaneous 24 weekly injections..
Total Total of all reporting groups

Baseline Measures
    Arm A: BIM 23A760 1 mg     Arm B: BIM 23A760 2 mg     Arm C: BIM 23A760 4 mg     Arm D: BIM 23A760 6 mg     Total  
Number of Participants  
[units: participants]
  19     19     18     20     76  
Age  
[units: Years]
Mean (Standard Deviation)
  42.8  (11.3)     48.7  (11.2)     40.3  (11.3)     43.4  (12.9)     43.8  (11.9)  
Gender  
[units: Participants]
         
Female     10     13     6     13     42  
Male     9     6     12     7     34  
Race/Ethnicity, Customized  
[units: Participants]
         
Caucasian/White     17     14     13     18     62  
Multiple race     2     5     5     2     14  
Region of Enrollment [1]
[units: Participants]
         
Belgium     1     1     0     0     2  
Brazil     1     1     3     5     10  
Czech Republic     1     1     0     1     3  
Lithuania     1     1     3     1     6  
Mexico     2     4     4     1     11  
Netherlands     2     0     0     1     3  
Poland     1     1     0     0     2  
Romania     4     3     1     4     12  
Ukraine     6     4     4     6     20  
France     0     1     0     1     2  
United States     0     2     1     0     3  
Latvia     0     0     1     0     1  
Sweden     0     0     1     0     1  
Height  
[units: cm]
Mean (Standard Deviation)
  170.1  (8.1)     170.3  (13.2)     175.0  (10.1)     166.4  (8.6)     170.3  (10.4)  
Diabetic status at entry  
[units: Participants]
         
Diabetic     2     1     2     2     7  
Non-diabetic     17     18     16     18     69  
Insulin-like growth factor 1 (IGF-1)  
[units: Percentage of ULN(Upper limit of number)]
Median (Full Range)
  307  
  (146 to 690)  
  315  
  (176 to 508)  
  382  
  (168 to 549)  
  335  
  (157 to 539)  
  333  
  (146 to 690)  
Growth Hormone (GH)  
[units: ng/mL]
Mean (Standard Deviation)
  16.79  (24.56)     20.99  (59.28)     28.60  (64.83)     26.59  (63.47)     23.21  (55.54)  
Baseline Prolactin  
[units: μg/L]
Mean (Standard Deviation)
         
Males (n=A:9,B:6,C:12, D:7, and Total:34)     11.506  (14.233)     34.113  (49.588)     41.657  (60.965)     83.036  (131.024)     40.86  (72.52)  
Pre-menopausal female(n=A:4,B:4,C:4,D:7,&Totl:19)     19.838  (15.247)     26.158  (19.798)     35.608  (25.536)     23.634  (23.778)     25.88  (21.94)  
Post-menopausal female(n=A:6,B:9,C:2,D:6,&Totl:23)     8.420  (3.167)     16.409  (24.232)     7.870  (0.693)     25.118  (39.986)     15.85  (25.89)  
Ring Finger Circumference  
[units: mm]
Mean (Standard Deviation)
  70.2  (5.6)     68.5  (6.2)     71.2  (4.7)     68.4  (6.3)     69.53  (5.75)  
[1] ITT population



  Outcome Measures
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1.  Primary:   Percentage of Subjects With Mean GH ≤2.5 ng/mL and Normalised IGF-1   [ Time Frame: At Month 6 ]

2.  Secondary:   Percentage of Subjects With Mean GH ≤2.5 ng/mL and Normalised IGF-1   [ Time Frame: At Month 3 ]

3.  Secondary:   Percentage of Subjects With Mean GH ≤2.5 ng/mL and Normalised IGF-1   [ Time Frame: At Month 1 ]

4.  Secondary:   Percent Change From Baseline in the Mean GH From 0-3 Hours at Months 1, 3 and 6   [ Time Frame: 0-3 hr on Baseline (Day 1) and Months 1, 3 and 6 ]

5.  Secondary:   Changes in IGF-1   [ Time Frame: Baseline (Day 1) and Month 6 ]

6.  Secondary:   Percentage Change in Ring Finger Circumference   [ Time Frame: Baseline (Day 1) and Month 6 ]

7.  Secondary:   Number of Subjects Reported Adverse Events During the Study   [ Time Frame: Up to Visit 10 (An average of 6.5 Months) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was terminated prematurely due to lack of efficacy.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Medical Director, Endocrinology
Organization: Ipsen
phone: clinical.trials@ipsen.com
e-mail: clinical.trials@ipsen.com



Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT00994214     History of Changes
Other Study ID Numbers: 2-55-52060-003
Study First Received: October 13, 2009
Results First Received: October 14, 2015
Last Updated: January 7, 2016
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Czech Republic: State Institute for Drug Control
Lithuania: State Medicine Control Agency - Ministry of Health
Latvia: State Agency of Medicines
Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Romania: National Medicines Agency
Ukraine: State Pharmacological Center - Ministry of Health
Italy: The Italian Medicines Agency
Mexico: Ethics Committee
Brazil: Ethics Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Canada: Health Products and Food Branch (HPFB)