Once-daily Oral Modified Release Hydrocortisone in Patients With Adrenal Insufficiency (DC 06/02)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00915343
First received: June 5, 2009
Last updated: July 16, 2015
Last verified: March 2014
Results First Received: June 8, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Adrenal Insufficiency
Interventions: Drug: hydrocortisone (modified release), oral tablet 20 and 5 mg
Drug: Hydrocortisone, oral tablet, 10 mg

  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
Study consisted of Part A (cross-over) and Part B (open-label). Of the 64 participants started and completed Part A, 5 participants did not enter Part B (treatment switch=2, withdrawal by participant= 2, nausea and abnormal laboratory value=1), 59 started Part B of the study.

Reporting Groups
  Description
Hydrocortisone MR OD Then Hydrocortisone TID - Part A Participants received novel once daily (OD) hydrocortisone modified release (MR) tablets in the first intervention period then hydrocortisone tablets thrice daily (TID) in the second intervention period, at the same total daily dose of 20 to 40 milligram (mg) for 12 weeks.
Hydrocortisone TID Then Hydrocortisone MR OD - Part A Participants received hydrocortisone tablets TID in the first intervention period then novel OD hydrocortisone MR tablets in the second intervention period, at the same total daily dose of 20 to 40 mg for 12 weeks.
Hydrocortisone MR Tablet OD - Part B (All 6 Months) Hydrocortisone MR tablets 20 to 40 mg orally OD for 6 months.

Participant Flow for 3 periods

Period 1:   Part A - First Intervention Period
    Hydrocortisone MR OD Then Hydrocortisone TID - Part A     Hydrocortisone TID Then Hydrocortisone MR OD - Part A     Hydrocortisone MR Tablet OD - Part B (All 6 Months)  
STARTED     32     32     0  
COMPLETED     32     32     0  
NOT COMPLETED     0     0     0  

Period 2:   Part A - Second Intervention Period
    Hydrocortisone MR OD Then Hydrocortisone TID - Part A     Hydrocortisone TID Then Hydrocortisone MR OD - Part A     Hydrocortisone MR Tablet OD - Part B (All 6 Months)  
STARTED     32     32     0  
COMPLETED     32     32     0  
NOT COMPLETED     0     0     0  

Period 3:   Part B - Open Label Period
    Hydrocortisone MR OD Then Hydrocortisone TID - Part A     Hydrocortisone TID Then Hydrocortisone MR OD - Part A     Hydrocortisone MR Tablet OD - Part B (All 6 Months)  
STARTED     0     0     59  
COMPLETED     0     0     57  
NOT COMPLETED     0     0     2  
Treatment switch                 0                 0                 1  
Did not attend the last visit                 0                 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.
Intention-To-Treat (ITT) set included all randomised participants who took at least 1 dose of study drug with assessments of any variables or with primary efficacy assessments including all pharmacokinetic (PK) samplings during any of the treatment periods.

Reporting Groups
  Description
Entire Study Included all participants randomized to receive hydrocortisone MR tablets orally OD first or hydrocortisone tablets orally TID first; in any of the intervention periods during the 12-week cross-over period of Part A or hydrocortisone MR tablets orally OD during the 6-month open-label period of Part B.

Baseline Measures
    Entire Study  
Number of Participants  
[units: participants]
  63  
Age  
[units: years]
Mean (Standard Deviation)
  47.3  (13.7)  
Gender  
[units: participants]
 
Female     26  
Male     37  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Area Under the Concentration Time Curve From Zero to 24 Hours (AUC0-24h) of Total S-cortisol in Plasma After Multiple Doses During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

2.  Secondary:   Maximal Concentration (Cmax1) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

3.  Secondary:   Maximal Concentration (Cmax2) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

4.  Secondary:   Average Concentration of S-cortisol During the Dosing Interval at Steady State (Css,av) in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

5.  Secondary:   First Detectable Concentration (Cfirst) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

6.  Secondary:   Concentration at 6 Hours (C6h) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

7.  Secondary:   Concentration at 7 Hours (C7h) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

8.  Secondary:   Time to Peak Plasma Concentration (Tmax1) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

9.  Secondary:   Time to Peak Plasma Concentration (Tmax2) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

10.  Secondary:   Time to First Detectable Concentration (Tfirst) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

11.  Secondary:   Time to Reach a Concentration of 200 Nanometers (nM) (T200) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

12.  Secondary:   Drug Concentration Half-Life From 5 to 24 Hours (t1/2[5-24h]) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

13.  Secondary:   Drug Concentration Half-Life From 5 to 14 Hours (t1/2[5-14h]) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

14.  Secondary:   Area Under the Concentration Time Curve (AUC) Between Specified Timepoints of Total S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

15.  Secondary:   Area Under the Concentration Time Curve During a Dosing Interval at Steady State (AUCtau) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

16.  Secondary:   Area Under the Concentration Time Curve During a Dosing Interval at Steady State Adjusted by Dose (AUCtau/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

17.  Secondary:   Area Under the Concentration Time Curve From Zero to 24 Hours Adjusted by Dose (AUC0-24h/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

18.  Secondary:   Area Under the Concentration Time Curve From Zero to 10 Hours Adjusted by Dose (AUC0-10h/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

19.  Secondary:   Area Under the Concentration Time Curve From Zero to 4 Hours Adjusted by Dose (AUC0-4h/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

20.  Secondary:   Average Concentration of S-cortisol During the Dosing Interval at Steady State Adjusted by Dose (Css,av/Dose) in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

21.  Secondary:   Maximal Concentration Adjusted by Dose (Cmax1/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

22.  Secondary:   Time to First Detectable Concentration Adjusted by Dose (Tfirst/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

23.  Secondary:   First Detectable Concentration Adjusted by Dose (Cfirst/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

24.  Secondary:   Percentage (%) of Area Under the Concentration Time Curve (AUC) Extrapolation of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

25.  Secondary:   Percentage (%) of Fluctuation in Concentrations of S-cortisol at Steady State in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

26.  Secondary:   Accumulation Ratio (Rac) of S-cortisol in Plasma After Single and Multiple Dosing During Part A   [ Time Frame: Arm 1: Week 4, Week 16, Week 16 + 1 day, Week 28; Arm 2: Week 4, Week 4 + 7 days, Week 16, Week 16 + 7 days ]

27.  Secondary:   Comparison of Overall Patient Tolerability Score Between Once Daily and Thrice Daily Therapy, Assessed by Patient and Investigator – Part A   [ Time Frame: 12 weeks ]

28.  Secondary:   Percentage (%) of Participants With Change From Baseline in Patient Tolerability Questionnaire at Month 6, Assessed by Patient and Investigator – Part B   [ Time Frame: Baseline (week 0), month 6 ]

29.  Secondary:   Comparison of Quality of Life (QoL) Assessed by Short Form-36 Survey (SF-36) For Physical and Mental Component Score Between Once Daily and Thrice Daily Therapy- Part A   [ Time Frame: 12 weeks ]

30.  Secondary:   Change From Baseline to 6 Months in Quality of Life (QoL) Assessed by Short Form-36 Survey (SF-36) For Physical and Mental Component Score - Part B   [ Time Frame: Baseline (week 0), month 6 ]

31.  Secondary:   Comparison of Quality of Life (QoL) Assessed by Fatigue Impact Scale (FIS) Total Score Between Once Daily and Thrice Daily Therapy - Part A   [ Time Frame: 12 weeks ]

32.  Secondary:   Change From Baseline to 6 Months in Quality of Life (QoL) Assessed by Fatigue Impact Scale (FIS) Total Score - Part B   [ Time Frame: Baseline (week 0), month 6 ]

33.  Secondary:   Comparison of Quality of Life (QoL) Assessed by Psychological General Well Being (PGWB) Total Scores Between Once Daily and Thrice Daily Therapy- Part A   [ Time Frame: 12 weeks ]

34.  Secondary:   Change From Baseline to 6 Months in Quality of Life (QoL) Assessed by Psychological General Well Being (PGWB) Total Scores- Part B   [ Time Frame: Baseline (week 0), month 6 ]

35.  Secondary:   Change From Baseline to 12 Weeks in Diurnal Fatigue Questionnaire for Day Average of Once Daily Therapy - Part A   [ Time Frame: Baseline (week 0), Week 12 ]

36.  Secondary:   Change From Baseline to 6 Months in Diurnal Fatigue Questionnaire for Day Average- Part B   [ Time Frame: Baseline (week 0), month 6 ]

37.  Secondary:   Comparison on Participant Compliance Between Once Daily and Thrice Daily Therapy - Part A   [ Time Frame: Weeks 4 up to 28 ]

38.  Secondary:   Participant Compliance- Part B   [ Time Frame: Up to Month 6 follow-up ]

39.  Secondary:   Comparison on Participant Preference by Questionnaire Between Once Daily and Thrice Daily Therapy-Part A   [ Time Frame: Weeks 16 up to 28 ]

40.  Secondary:   Comparison on 24-hour Urinary Free Cortisol Between Once Daily and Thrice Daily Therapy-Part A   [ Time Frame: 12 weeks ]


  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: Study Physician
Organization: Shire
phone: 1866-842-5335


Publications:


Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00915343     History of Changes
Other Study ID Numbers: EudraCT: 2006-0007084-89, 104-07
Study First Received: June 5, 2009
Results First Received: June 8, 2015
Last Updated: July 16, 2015
Health Authority: Europe: European Medicines Agency (EMEA)