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Extension Study of Protocol DFA102 to Examine the Long-Term Safety, Tolerability, and Effect on Body Weight of Pramlintide Administered in Combination With Metreleptin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00819234
First received: December 24, 2008
Last updated: June 6, 2014
Last verified: November 2013
Results First Received: August 12, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Obesity
Interventions: Drug: Placebo
Drug: Pramlintide and Metreleptin

  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
Participants (overweight and obese) must have been randomized and treated in original DFA102 Study (NCT00673387) in order to be enrolled into this extension study DFA102E and followed for a total of up to 52 weeks, inclusive of DFA102 (ie, DFA102 and DFA102E studies together have a total length of 52 weeks).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
DFA102 participants assigned to: placebo, 360mcg pramlintide+1.25mg metreleptin, 360mcg pram+2.5mg metre, or 360mcg pram+5.0mg metre did not change treatment in extension (stable groups). All other groups transitioned to 360mcg pram + 1.25, 2.5 or 5.0mg metre. 274 enrolled in extension and 273 were treated.

Reporting Groups
  Description
Placebo - Stable

Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102.

Stable: same treatment regimen in both DFA102 and DFA102E.

360 mcg Pramlintide + 1.25mg Metreleptin - Stable

Participants who received 360 mcg pramlintide plus 1.25 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102.

Stable: same treatment regimen in both DFA102 and DFA102E

360 mcg Pramlintide + 2.5 Metreleptin - Stable

Participants who received 360 mcg pramlintide plus 2.5 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102.

Stable: same treatment regimen in both DFA102 and DFA102E

360 mcg Pramlintide + 5.0 Metreleptin - Stable

Participants who received 360 mcg pramlintide plus 5.0 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102.

Stable: same treatment regimen in both DFA102 and DFA102E.

360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Monotherapy Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study for up to 52 Weeks, inclusive of DFA102.
360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Monotherapy Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study for up to 52 Weeks, inclusive of DFA102.
360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Monotherapy Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study for up to 52 Weeks, inclusive of DFA102.
360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.

Participant Flow:   Overall Study
    Placebo - Stable     360 mcg Pramlintide + 1.25mg Metreleptin - Stable     360 mcg Pramlintide + 2.5 Metreleptin - Stable     360 mcg Pramlintide + 5.0 Metreleptin - Stable     360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Monotherapy     360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Monotherapy     360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Monotherapy     360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono     360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram     360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram  
STARTED     31     35     36     28     13     14     13     29     37     37  
COMPLETED     21     20     28     22     12     7     8     20     31     30  
NOT COMPLETED     10     15     8     6     1     7     5     9     6     7  
Withdrawal by Subject                 8                 13                 6                 3                 0                 4                 4                 8                 5                 3  
Adverse Event                 0                 0                 1                 0                 0                 2                 0                 0                 0                 0  
Physician Decision                 0                 0                 0                 1                 0                 0                 0                 0                 0                 2  
Protocol Violation                 0                 0                 1                 0                 0                 0                 0                 0                 0                 0  
Lost to Follow-up                 2                 2                 0                 2                 1                 1                 1                 1                 1                 2  



  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.
All participants who completed original study and chose to be enrolled into this extension study and were treated with study drug.

Reporting Groups
  Description
All Participants All participants who completed the original study and chose to enter the extension study.

Baseline Measures
    All Participants  
Number of Participants  
[units: participants]
  273  
Age  
[units: years]
Mean ± Standard Deviation
  47.3  ± 10.27  
Gender  
[units: participants]
 
Female     191  
Male     82  
Region of Enrollment  
[units: participants]
 
United States     273  
Body Weight at Baseline [1]
[units: kilograms]
Mean ± Standard Deviation
  95.83  ± 17.007  
Body Mass Index (BMI) at Baseline [2]
[units: kg/m^2]
Mean ± Standard Deviation
  34.16  ± 4.988  
[1] Baseline in the extension study was Week 28 in the original study. If Week 28 value was missing or after the first dose in DFA102E, the last available value on or prior to Week 28 was used.
[2] Baseline refers to Week 28 in original study. If Week 28 was missing or after the first dose in DFA102E, the last available value on or prior to Week 28 was used. Body Mass Index (BMI) was measured as kilogram per meter of height squared (kg/m^2).



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   LS Mean Percent Change in Body Weight From Original Study DFA102 (NCT00673387) Baseline (Day 1) at Week 52 in Extension Study DFA102E - Evaluable Treatment Stable Population   [ Time Frame: Original Study Baseline to Week 52 ]

2.  Secondary:   LS Mean Absolute Change in Body Weight From Original Study Baseline (Day 1) at Weeks 12, 28, 36, 44, and 52 - Evaluable Treatment Stable Population   [ Time Frame: Original baseline to Week 52 ]

3.  Secondary:   Fasting Total Leptin Concentration by Visit and Pooled Metreleptin Stable Treatment by Metreleptin Dose - Week 52 Stable Evaluable Population   [ Time Frame: Original Study Baseline to Extension Week 52 and follow up ]

4.  Secondary:   LS Mean Absolute Change in Waist Circumference From Baseline in the Original Study to Week 52 in the Extension Study - Week 52 Evaluable Stable Population   [ Time Frame: Baseline to Week 52 ]

5.  Secondary:   LS Mean Percent Change in Body Weight From Baseline of Original Study DFA102 at Week 12, and at Weeks 28, 36, 44, and 52 in the Extension Study DFA102E - Week 52 Evaluable Treatment Stable Population   [ Time Frame: Baseline to Week 52 ]

6.  Secondary:   LS Mean Absolute Change From Baseline in Original Study DFA102 to Week 52 in Extension Study DFA102E for Glucose and Lipids - Week 52 Evaluable Treatment Stable Population   [ Time Frame: Baseline (Day 1) to Week 52 ]

7.  Secondary:   LS Mean Absolute Change From Baseline in Original Study DFA102 to Week 52 in Extension Study DFA102E in Total Insulin - Week 52 Evaluable Treatment Stable Population   [ Time Frame: Baseline to Week 52 ]

8.  Secondary:   Number of Participants Achieving at Least 5%, 10%, and 15% of Body Weight Loss From Original Study DFA102 Baseline to Week 52 in Extension Study DFA102E - Week 52 Evaluable Population   [ Time Frame: Baseline (Day 1) to Week 52 ]

9.  Secondary:   Number of Participants Achieving at Least 5%, 10% and 15% Body Weight Loss From Extension Study DFA102E Baseline (Week 28) to Week 52 - Week 52 Evaluable Population   [ Time Frame: Baseline (Week 28) to Week 52 ]

10.  Secondary:   Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores – Week 52 Evaluable Population   [ Time Frame: Screening to Week 52 ]

11.  Secondary:   Mean Absolute Change From Original Study DFA102 Screening to Week 52 in Extension Study DFA102E in Binge Eating Scale (BES) Total Score - Week 52 Evaluable Population   [ Time Frame: Screening to Week 52 ]

12.  Secondary:   Mean Absolute Change From Original Study DFA102 Screening to Week 52 in Extension Study DFA102E in Hospital Anxiety and Depression Scale (HADS) Total Scores – Week 52 Evaluable Population   [ Time Frame: Screening to Week 52 ]

13.  Secondary:   Mean Absolute Change From Original Study DFA102 Screening to Week 52 in Extension Study DFA102E in the Epworth Sleepiness Scale (ESS) Total Score – Week 52 Evaluable Population   [ Time Frame: Screening to Week 52 ]

14.  Secondary:   Total Trough Concentration of Plasma Leptin at Baseline and at Weeks 40, 52, and End of Treatment Follow up - Week 52 Stable Evaluable Population   [ Time Frame: Baseline to end of treatment follow up ]

15.  Secondary:   Mean Change in Systolic and Diastolic Blood Pressure From Baseline of DFA102 at Week 52 of DFA102E - Intent to Treat Population   [ Time Frame: Baseline (Day 1) to Week 52 ]

16.  Secondary:   Mean Change in Heart Rate From Baseline of DFA102 at Week 52 of DFA102E - Intent to Treat Population   [ Time Frame: Baseline to Week 52 ]

17.  Secondary:   Mean Change From DFA102 Screening at Week 52 in Study DFA102E for Electrocardiogram Parameters - Intent to Treat Population   [ Time Frame: Screening to Week 52 ]

18.  Secondary:   Number of Hematology or Urinalysis Laboratory Values of Potential Clinical Importance Observed From Baseline of DFA102E to Week 52 - Intent to Treat Population   [ Time Frame: Baseline to Week 52 ]

19.  Secondary:   Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From DFA102E Baseline to Week 52 - Intent to Treat Population   [ Time Frame: Baseline to Week 52 ]

20.  Secondary:   Number of Participants With Treatment Emergent Positive Anti-leptin Antibody Titers at Week 52 and at Follow up by Metreleptin Dose - Intent to Treat Population   [ Time Frame: Baseline to end of treatment follow up ]


  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
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  More Information
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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: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided


Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00819234     History of Changes
Other Study ID Numbers: DFA102E
Study First Received: December 24, 2008
Results First Received: August 12, 2013
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration