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Efficacy and Safety of Pasireotide Long Acting Release (LAR) Versus Octreotide LAR or Lanreotide Autogel (ATG) in Patients With Inadequately Controlled Acromegaly (PAOLA)

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ClinicalTrials.gov Identifier: NCT01137682
Recruitment Status : Completed
First Posted : June 4, 2010
Results First Posted : January 21, 2015
Last Update Posted : April 5, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Acromegaly
Interventions: Drug: Pasireotide
Drug: octreotide LAR 30mg
Drug: lanreotide ATG 120mg

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
One hundred ninety-eight patients were randomized and 5 patients in CORE and 1 patient in extension did not receive any study treatment

Reporting Groups
  Description
Pasireotide LAR 40 mg Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days
Pasireotide LAR 60 mg Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution) for intramuscular administration every 28 days
Control Arm (Octreotide or Lanreotide) Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days

Participant Flow:   Overall Study
    Pasireotide LAR 40 mg   Pasireotide LAR 60 mg   Control Arm (Octreotide or Lanreotide)
STARTED   65   65   68 
Not Treated   2   2   1 
Treated   63   63   67 
Completed 24-Week Core Phase   59   57   65 
Not Continuing Into Extension   2   3   2 
Continuing Into Extension   57   54   63 
Safety Set - CORE   63 [1]   62 [2]   66 [1] 
Safety Set - Extension   57   54   62 [3] 
COMPLETED   28   25   34 
NOT COMPLETED   37   40   34 
Adverse Event-CORE                2                4                0 
Withdrawal by Subject-CORE                2                2                2 
Administrative problems-CORE                2                1                0 
Protocol Violation-CORE                0                1                1 
Adverse Event-Extension                4                8                7 
Lack of Efficacy-Extension                15                9                13 
Withdrawal by Subject-Extension                6                8                8 
Lost to Follow Up-Extension                0                1                0 
Administrative problems-Extension                0                2                0 
Death-Extension                2                0                0 
Protocol Violation-Extension                2                1                0 
Did not enter extension                2                3                2 
Did not receive treatment in extension                0                0                1 
[1] 2 patients never received drug.
[2] 2 patients never received drug. 1 patient had no post baseline safety assement.
[3] 1 patient did not receive study treatment



  Baseline Characteristics

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
Pasireotide LAR 40 mg Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)
Pasireotide LAR 60 mg Supplied in blinded fashion as 20 and 40 mg powder in vials and 2 mL vehicle in ampoule (for reconstitution)
Control Arm (Octreotide or Lanreotide) Open label octreotide LAR 30 mg or lanreotide ATG 120 mg supplied either locally or from designated depot. Administered intramuscular every 28 days
Total Total of all reporting groups

Baseline Measures
   Pasireotide LAR 40 mg   Pasireotide LAR 60 mg   Control Arm (Octreotide or Lanreotide)   Total 
Overall Participants Analyzed 
[Units: Participants]
 65   65   68   198 
Age, Customized [1] 
[Units: Participants]
       
<65 Years   62   57   63   182 
≥ 65 Years   3   8   5   16 
[1] CORE Period
Sex: Female, Male [1] 
[Units: Participants]
Count of Participants
       
Female      38  58.5%      35  53.8%      38  55.9%      111  56.1% 
Male      27  41.5%      30  46.2%      30  44.1%      87  43.9% 
[1] CORE Period
Race/Ethnicity, Customized [1] 
[Units: Participants]
       
Caucasian   53   52   56   161 
Black   3   8   4   15 
Other   4   3   7   14 
Native American   2   1   1   4 
Asian   3   1   0   4 
[1] CORE Period


  Outcome Measures

1.  Primary:   Percentage of Participants With a Reduction of Mean GH Levels to < 2.5 µg/L and Normalization of Sex- and Age-adjusted IGF-1.   [ Time Frame: At 24 weeks ]

2.  Secondary:   Percentage of Patients With Mean GH < 2.5 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)   [ Time Frame: Extension baseline up to approximately week 268 ]

3.  Secondary:   Percentage of Participants With Normalization of Sex- and Age-adjusted IGF-1treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set).   [ Time Frame: Extension baseline up to approximately week 268 ]

4.  Secondary:   Percentage of Patients With Mean GH < 2.5 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)   [ Time Frame: Extension baseline up to approximately week 268 ]

5.  Secondary:   Percentage of Patients With Mean GH < 1.0 μg/L and Normalization of IGF-1, Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)   [ Time Frame: Extension baseline up to approximately week 268 ]

6.  Secondary:   Percentage of Patients With Mean GH <1.0 μg/L Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)   [ Time Frame: Extension baseline up to approximately week 268 ]

7.  Secondary:   Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set)   [ Time Frame: CORE baseline up to approximately 24 weeks ]

8.  Secondary:   Change From Baseline in Mean GH Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set)   [ Time Frame: CORE and extension baseline up to approximately 268 weeks ]

9.  Secondary:   Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits (Extension Full Analysis Set)   [ Time Frame: CORE baseline up to approximately 24 weeks ]

10.  Secondary:   Change From Baseline in Standardized IGF-1 Values for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set)   [ Time Frame: CORE and extension baseline up to approximately 268 weeks ]

11.  Secondary:   Duration of the First Response for Patients Achieving a Reduction of Mean GH Level to < 2.5 μg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly (Extension Full Analysis Set)   [ Time Frame: CORE baseline up to approximately 268 weeks ]

12.  Secondary:   Time to First Response (Weeks) by Treatment for Patients Achieving a Reduction of Mean GH Level to < 2.5 µg/L and Normalization of IGF-1 and Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly   [ Time Frame: CORE baseline up to approximately 268 weeks ]

13.  Secondary:   Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for CORE Visits(Extension Full Analysis Set)   [ Time Frame: CORE baseline up to approximately 24 weeks ]

14.  Secondary:   Change From Baseline in AcroQoL Total Scores for Patients Treated With Pasireotide LAR Alone or With Concomitant Medications Used to Treat Acromegaly for Extension Visits (Extension Full Analysis Set)   [ Time Frame: CORE Baseline and extension baseline up to approximately 268 weeks ]

15.  Secondary:   Summary of Pasireotide Trough Concentrations in Acromegaly Patients Following Monthly i.m. Injections of Pasireotide LAR by Incident Dose From Start of Extension Phase up to Week 196 of the Extension Phase (PK Set)   [ Time Frame: Extension baseline up to approximately 196 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

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
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: Novartis.email@novartis.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01137682     History of Changes
Other Study ID Numbers: CSOM230C2402
EUDRACT 2009-016722-13 ( Registry Identifier: EUDRACT )
First Submitted: May 27, 2010
First Posted: June 4, 2010
Results First Submitted: January 13, 2015
Results First Posted: January 21, 2015
Last Update Posted: April 5, 2018