Phase 3
N=64
Once-daily Oral Modified Release Hydrocortisone in Patients With Adrenal Insufficiency
Adrenal Insufficiency
Bottom Line
View on ClinicalTrials.gov: NCT00915343 ↗Enrolled (actual)
64
Serious AEs
6.6%
Results posted
Jul 2015
Primary outcome: 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 — 3962.0; 4879.6 hour*nanomole per liter — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- hydrocortisone (modified release), oral tablet 20 and 5 mg (Drug); Hydrocortisone, oral tablet, 10 mg (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Shire
- Primary completion
- Jul 2008
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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 |
3962.0; 4879.6 | <0.0001 sig |
| SECONDARY Maximal Concentration (Cmax1) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
690.7; 802.8 | <0.0001 sig |
| SECONDARY Maximal Concentration (Cmax2) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
553.8; 446.9 | 0.0357 sig |
| 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 |
165.1; 203.3 | <0.0001 sig |
| SECONDARY First Detectable Concentration (Cfirst) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
229.0; 295.1 | 0.0033 sig |
| SECONDARY Concentration at 6 Hours (C6h) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
278.5; 426.7 | <0.0001 sig |
| SECONDARY Concentration at 7 Hours (C7h) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
214.1; 322.4 | <0.0001 sig |
| SECONDARY Time to Peak Plasma Concentration (Tmax1) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
1.00; 0.750 | 0.0214 sig |
| SECONDARY Time to Peak Plasma Concentration (Tmax2) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
5.00; 6.00 | 0.0714 |
| SECONDARY Time to First Detectable Concentration (Tfirst) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
0.229; 0.208 | 0.6687 |
| SECONDARY Time to Reach a Concentration of 200 Nanometers (nM) (T200) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
0.250; 0.167 | 0.0280 sig |
| 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 |
7.32; 1.84 | 0.0003 sig |
| 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 |
4.60; 18.4 | <0.0001 sig |
| 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 |
2053.7; 1929.7; 1491.8; 2302.5; 808.2; 1607.6 | 0.0002 sig |
| 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 |
3962.0; 4879.6 | <0.0001 sig |
| 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 |
0.048; 0.061 | <0.0001 sig |
| 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 |
0.047; 0.060 | <0.0001 sig |
| 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 |
0.041; 0.046 | <0.0001 sig |
| 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 |
0.025; 0.024 | 0.0020 sig |
| 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 |
0.002; 0.003 | <0.0001 sig |
| SECONDARY Maximal Concentration Adjusted by Dose (Cmax1/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
0.008; 0.010 | <0.0001 sig |
| SECONDARY Time to First Detectable Concentration Adjusted by Dose (Tfirst/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
2.26; 2.32 | 0.7827 |
| SECONDARY First Detectable Concentration Adjusted by Dose (Cfirst/Dose) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
0.003; 0.004 | 0.0015 sig |
| SECONDARY Percentage (%) of Area Under the Concentration Time Curve (AUC) Extrapolation of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
10.1; 9.26 | <0.0001 sig |
| SECONDARY Percentage (%) of Fluctuation in Concentrations of S-cortisol at Steady State in Plasma After Single and Multiple Dosing During Part A |
429.7; 396.2 | 0.0396 sig |
| SECONDARY Accumulation Ratio (Rac) of S-cortisol in Plasma After Single and Multiple Dosing During Part A |
1.11; 1.03 | 0.1032 |
| SECONDARY Comparison of Overall Patient Tolerability Score Between Once Daily and Thrice Daily Therapy, Assessed by Patient and Investigator - Part A |
4.28; 4.36; 4.26; 4.33 | 0.3767 |
| SECONDARY Percentage (%) of Participants With Change From Baseline in Patient Tolerability Questionnaire at Month 6, Assessed by Patient and Investigator - Part B |
10.7; 14.0; 73.2; 70.0; 16.1; 16.0 | 0.6072 |
| 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 |
49.3; 50.0; 51.1; 49.8 | 0.3332 |
| 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 |
0.390; -0.896 | 0.8418 |
| SECONDARY Comparison of Quality of Life (QoL) Assessed by Fatigue Impact Scale (FIS) Total Score Between Once Daily and Thrice Daily Therapy - Part A |
22.6; 26.4 | 0.0823 |
| SECONDARY Change From Baseline to 6 Months in Quality of Life (QoL) Assessed by Fatigue Impact Scale (FIS) Total Score - Part B |
-1.09 | 0.5982 |
| 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 |
110.5; 107.7 | 0.0632 |
| SECONDARY Change From Baseline to 6 Months in Quality of Life (QoL) Assessed by Psychological General Well Being (PGWB) Total Scores- Part B |
-0.739 | 0.8676 |
| SECONDARY Change From Baseline to 12 Weeks in Diurnal Fatigue Questionnaire for Day Average of Once Daily Therapy - Part A |
-3.1 | 0.9700 |
| SECONDARY Change From Baseline to 6 Months in Diurnal Fatigue Questionnaire for Day Average- Part B |
-0.180 | 0.2624 |
| SECONDARY Comparison on Participant Compliance Between Once Daily and Thrice Daily Therapy - Part A |
104.8; 103.1 | — |
| SECONDARY Participant Compliance- Part B |
102.3 | — |
| SECONDARY Comparison on Participant Preference by Questionnaire Between Once Daily and Thrice Daily Therapy-Part A |
3.8; 5.7; 5.7; 20.8; 64.2; 3.7 | <0.0001 sig |
| SECONDARY Comparison on 24-hour Urinary Free Cortisol Between Once Daily and Thrice Daily Therapy-Part A |
385.7; 425.9 | 0.0034 sig |
Summary
This is a randomised, controlled, open, two-armed, two-period cross-over, multi-centre phase II/III study to assess the safety, tolerability and pharmacokinetics of once-daily oral modified-release hydrocortisone in comparison to conventional thrice-daily oral hydrocortisone tablets in patients with adrenal insufficiency
Eligibility Criteria
Inclusion Criteria
- Previously diagnosed (e.g. more than 6 months ago) primary adrenal insufficiency with a stable daily glucocorticoid substitution dose for at least 3 months prior to study entry
- Signed informed consent to participate in the study.
Exclusion Criteria
- Clinical or laboratory signs of significant cerebral, cardiovascular, respiratory, Hepatobiliary, pancreatic disease
- Clinically significant renal dysfunction
- Clinical or laboratory signs of significant gastrointestinal emptying or motility disease
- Any medication with agents which could interfere with hydrocortisone kinetics
- Pregnant or lactating women
- Regular dehydroepiandrosterone (DHEA) medication for the past 4 weeks
- Oral oestrogen medication for the past 4 weeks
- Deranged mineralocorticoid status
Data sourced from ClinicalTrials.gov (NCT00915343). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.