Study Assessing the PK of EFB0027 (Metformin Delayed-release) and Effect on Circulating Glucose and GI Hormone Concentrations in Subjects With T2DM

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Elcelyx Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01677299
First received: August 23, 2012
Last updated: May 15, 2014
Last verified: May 2014
Results First Received: February 12, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Basic Science
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: EFB0027 (metformin delayed release)
Drug: EFB0026 (metformin immediate-release)

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Sequence 1: BCAD

BID

Treatment A = 1000 mg EFB0026 (Met Immediate Release) Treatment B = 1000 mg EFB0027 (Met Delayed Release) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)

Sequence 2: ABDC

BID

Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)

Sequence 3: CDBA

BID

Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)

Sequence 4: DACB

BID

Treatment A = 1000 mg EFB0026 (Met IR) Treatment B = 1000 mg EFB0027 (Met DR) Treatment C = 500 mg EFB0027 (Met DR) Treatment D = 500 mg EFB0026 (Met IR) plus 1000 mg EFB0027 (Met DR)


Participant Flow:   Overall Study
    Sequence 1: BCAD     Sequence 2: ABDC     Sequence 3: CDBA     Sequence 4: DACB  
STARTED     6     6     6     6  
COMPLETED     6     3     5     5  
NOT COMPLETED     0     3     1     1  
Adverse Event                 0                 2                 1                 0  
Withdrawal by Subject                 0                 1                 0                 1  



  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
Sequence BCAD A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID
Sequence ABDC A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID
Sequence CDBA A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID
Sequence DACB A = 1000 mg EFB0026 BID B = 1000 mg EFB0027 BID C = 500 mg EFB0027 BID D = 500 mg EFB0026 BID plus 1000 mg EFB0027 BID
Total Total of all reporting groups

Baseline Measures
    Sequence BCAD     Sequence ABDC     Sequence CDBA     Sequence DACB     Total  
Number of Participants  
[units: participants]
  6     6     6     6     24  
Age  
[units: years]
Mean ± Standard Deviation
  43.2  ± 3.54     56.8  ± 7.22     49.7  ± 13.92     55.3  ± 7.79     51.3  ± 9.98  
Gender  
[units: participants]
         
Female     2     3     3     4     12  
Male     4     3     3     2     12  
Race (NIH/OMB)  
[units: participants]
         
American Indian or Alaska Native     0     0     0     0     0  
Asian     0     3     0     0     3  
Native Hawaiian or Other Pacific Islander     0     0     0     0     0  
Black or African American     1     0     0     1     2  
White     5     3     6     5     19  
More than one race     0     0     0     0     0  
Unknown or Not Reported     0     0     0     0     0  
Ethnicity (NIH/OMB)  
[units: participants]
         
Hispanic or Latino     4     3     5     2     14  
Not Hispanic or Latino     2     3     1     4     10  
Unknown or Not Reported     0     0     0     0     0  
Region of Enrollment  
[units: participants]
         
United States     6     6     6     6     24  
BMI  
[units: kg/mˆ2]
Mean ± Standard Deviation
  34.13  ± 5.455     30.67  ± 2.793     35.65  ± 2.935     32.87  ± 3.644     33.33  ± 4.05  
eGFR  
[units: mL/min/1.73 mˆ2]
Mean ± Standard Deviation
  117.94  ± 22.065     114.65  ± 21.348     107.54  ± 16.644     93.43  ± 20.354     108.39  ± 21.161  
HbA1c  
[units: %]
Mean ± Standard Deviation
  7.62  ± 1.234     7.33  ± 0.965     8.07  ± 1.102     6.37  ± .339     7.35  ± 1.108  
FPG  
[units: mg/dL]
Mean ± Standard Deviation
  182.5  ± 71.55     158  ± 42.96     179  ± 69.59     124.3  ± 15.03     161  ± 56.34  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Area Under the Curve (0-t) of Plasma Metformin   [ Time Frame: pre-dose to 11 hours post-dose ]

2.  Primary:   Change in Fasting Plasma Glucose   [ Time Frame: Change from Baseline (Day 1) to Day 5 ]

3.  Primary:   Within Treatment Comparison Based on Ratios of AUCs of GLP-1   [ Time Frame: Ratio of Day 5 to Baseline ]
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Measure Type Primary
Measure Title Within Treatment Comparison Based on Ratios of AUCs of GLP-1
Measure Description No text entered.
Time Frame Ratio of Day 5 to Baseline  
Safety Issue No  

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.
Evaluable

Reporting Groups
  Description
1000 mg EFB0026

BID

EFB0026: Active comparator

1000 mg EFB0027

BID

EFB0027: Comparison of enteric-coating to assess effect on PK

500 mg EFB0027

BID

EFB0027: Comparison of enteric-coating to assess effect on PK

500 mg EFB0026 + 1000 mg EFB0027

BID

EFB0027: Comparison of enteric-coating to assess effect on PK

EFB0026: Active comparator


Measured Values
    1000 mg EFB0026     1000 mg EFB0027     500 mg EFB0027     500 mg EFB0026 + 1000 mg EFB0027  
Number of Participants Analyzed  
[units: participants]
  19     19     19     19  
Within Treatment Comparison Based on Ratios of AUCs of GLP-1  
[units: none (values are ratios)]
Least Squares Mean ± Standard Error
  1.87  ± 0.18     1.62  ± .11     1.69  ± .15     1.88  ± .19  


Statistical Analysis 1 for Within Treatment Comparison Based on Ratios of AUCs of GLP-1
Groups [1] 1000 mg EFB0027
Method [2] Mixed Models Analysis
P Value [3] <0.05
Geometric LS mean ration [4] 1.6
95% Confidence Interval ( 1.4 to 1.9 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Within Treatment Comparison Based on Ratios of AUCs of GLP-1
Groups [1] 1000 mg EFB0026
Method [2] Mixed Models Analysis
P Value [3] <0.05
Geo LSmean ratio of (Day 5/Baseline) [4] 1.9
95% Confidence Interval ( 1.5 to 2.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Within Treatment Comparison Based on Ratios of AUCs of GLP-1
Groups [1] 500 mg EFB0027
Method [2] Mixed Models Analysis
P Value [3] <0.05
Geo LSmean ratio (Day 5/Baseline) [4] 1.7
95% Confidence Interval ( 1.4 to 2.0 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Within Treatment Comparison Based on Ratios of AUCs of GLP-1
Groups [1] 500 mg EFB0026 + 1000 mg EFB0027
Method [2] Mixed Models Analysis
P Value [3] <0.05
Geo LSmean ratio (Day 5/Baseline) [4] 1.9
95% Confidence Interval ( 1.5 to 2.3 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



4.  Primary:   Within Treatment Comparison Based on Ratios of AUCs of PYY   [ Time Frame: Ratio of Day 5 to Baseline ]


  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: Senior Director, Development
Organization: Elcelyx Therapeutics, Inc
phone: 858-876-1814
e-mail: info@elcelyx.com


No publications provided


Responsible Party: Elcelyx Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01677299     History of Changes
Other Study ID Numbers: LCPOC10
Study First Received: August 23, 2012
Results First Received: February 12, 2014
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration