Trial Outcomes & Findings for Effect of Slow Release Hydrocortisone on Fed & Fasting Volunteers; Immediate Release on Fasting Only (NCT NCT02408068)
NCT ID: NCT02408068
Last Updated: 2022-05-04
Results Overview
Comparison of fed and fasted Chronocort Cmax for serum cortisol.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
24 hours
Results posted on
2022-05-04
Participant Flow
Participant milestones
| Measure |
Sequence 1
Chronocort 20mg (fed), Chronocort 20mg (fasted), Hydrocortisone 20mg (fasted)
|
Sequence 2
Chronocort 20mg (fed), Hydrocortisone 20mg (fasted), Chronocort 20mg (fasted)
|
Sequence 3
Chronocort 20mg (fasted), Chronocort 20mg (fed), Hydrocortisone 20mg (fasted)
|
Sequence 4
Chronocort 20mg (fasted), Hydrocortisone 20mg (fasted), Chronocort 20mg (fed)
|
Sequence 5
Hydrocortisone 20mg (fasted), Chronocort 20mg (fed), Chronocort 20mg (fasted)
|
Sequence 6
Hydrocortisone 20mg (fasted), Chronocort 20mg (fasted), Chronocort 20mg (fed)
|
|---|---|---|---|---|---|---|
|
Treatment 1 (1.5 Days)
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Treatment 1 (1.5 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Treatment 1 (1.5 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 1 (7 Days)
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Washout Period 1 (7 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Washout Period 1 (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment 2 (1.5 Days)
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Treatment 2 (1.5 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Treatment 2 (1.5 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 2 (7 Days)
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Washout Period 2 (7 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Washout Period 2 (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment 3 (1.5 Days)
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Treatment 3 (1.5 Days)
COMPLETED
|
3
|
3
|
2
|
3
|
3
|
3
|
|
Treatment 3 (1.5 Days)
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence 1
Chronocort 20mg (fed), Chronocort 20mg (fasted), Hydrocortisone 20mg (fasted)
|
Sequence 2
Chronocort 20mg (fed), Hydrocortisone 20mg (fasted), Chronocort 20mg (fasted)
|
Sequence 3
Chronocort 20mg (fasted), Chronocort 20mg (fed), Hydrocortisone 20mg (fasted)
|
Sequence 4
Chronocort 20mg (fasted), Hydrocortisone 20mg (fasted), Chronocort 20mg (fed)
|
Sequence 5
Hydrocortisone 20mg (fasted), Chronocort 20mg (fed), Chronocort 20mg (fasted)
|
Sequence 6
Hydrocortisone 20mg (fasted), Chronocort 20mg (fasted), Chronocort 20mg (fed)
|
|---|---|---|---|---|---|---|
|
Treatment 3 (1.5 Days)
Adverse Event
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Effect of Slow Release Hydrocortisone on Fed & Fasting Volunteers; Immediate Release on Fasting Only
Baseline characteristics by cohort
| Measure |
All Study Participants
n=18 Participants
All patients received all 3 study treatments in randomised order
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
34.0 years
STANDARD_DEVIATION 9.73 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
18 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 hoursPopulation: PK population: All randomised subjects who had sufficient plasma concentration by time profiles for 2 adequate treatments and who did not violate the protocol in such a way that could invalidate or bias the results (major protocol violators).
Comparison of fed and fasted Chronocort Cmax for serum cortisol.
Outcome measures
| Measure |
Chronocort Fed
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs and subsequently fast overnight. On the morning of Day 1, volunteers will eat a high fat breakfast and take 20mg of randomised treatment with 200 millilitres of water. Water will be allowed 1hr after the study drug is administered. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Chronocort Fasted
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Immediate-Release Hydrocortisone
n=14 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
|---|---|---|---|
|
Chronocort Cmax
|
549.49 nmol/L
Geometric Coefficient of Variation 17.4
|
708.46 nmol/L
Geometric Coefficient of Variation 19.3
|
856.36 nmol/L
Geometric Coefficient of Variation 14.6
|
PRIMARY outcome
Timeframe: 24 hours (at 0h, then 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h, 13h, 14h, 15h, 16h, 18h, 20h, 22h and 24h post-dose.)Population: PK population: All randomised subjects who had sufficient plasma concentration by time profiles for 2 adequate treatments and who did not violate the protocol in such a way that could invalidate or bias the results (major protocol violators).
Area under the curve from 0 to 24 hours for serum cortisol. Please note that the AUC0-t will be presented as a single figure (geometric mean) to represent exposure over time. N.B., the sampling points for Hydrocortisone are as follows: 0h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h and 12h post-dose. However, the results for Hydrocortisone will not be incorporated into the analysis for this outcome measure.
Outcome measures
| Measure |
Chronocort Fed
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs and subsequently fast overnight. On the morning of Day 1, volunteers will eat a high fat breakfast and take 20mg of randomised treatment with 200 millilitres of water. Water will be allowed 1hr after the study drug is administered. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Chronocort Fasted
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Immediate-Release Hydrocortisone
n=14 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
|---|---|---|---|
|
Comparison of Fed and Fasted Chronocort AUC0-t
|
3229.26 h*nmol/L
Geometric Coefficient of Variation 15.1
|
2980.85 h*nmol/L
Geometric Coefficient of Variation 14.3
|
2466.90 h*nmol/L
Geometric Coefficient of Variation 17.1
|
PRIMARY outcome
Timeframe: 24 hoursPopulation: PK population: All randomised subjects who had sufficient plasma concentration by time profiles for 2 adequate treatments and who did not violate the protocol in such a way that could invalidate or bias the results (major protocol violators).
Comparison of Fed and Fasted Chronocort based on the time to achive the maximum concentration of serum cortisol
Outcome measures
| Measure |
Chronocort Fed
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs and subsequently fast overnight. On the morning of Day 1, volunteers will eat a high fat breakfast and take 20mg of randomised treatment with 200 millilitres of water. Water will be allowed 1hr after the study drug is administered. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Chronocort Fasted
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Immediate-Release Hydrocortisone
n=14 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
|---|---|---|---|
|
Comparison of Fed and Fasted Chronocort Tmax
|
6.75 hours
Standard Deviation 3.62
|
4.5 hours
Standard Deviation 1.25
|
0.87 hours
Standard Deviation 0.81
|
PRIMARY outcome
Timeframe: 24 hoursPopulation: PK population: All randomised subjects who had sufficient plasma concentration by time profiles for 2 adequate treatments and who did not violate the protocol in such a way that could invalidate or bias the results (major protocol violators).
Evaluation of the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state by Cmax
Outcome measures
| Measure |
Chronocort Fed
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs and subsequently fast overnight. On the morning of Day 1, volunteers will eat a high fat breakfast and take 20mg of randomised treatment with 200 millilitres of water. Water will be allowed 1hr after the study drug is administered. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Chronocort Fasted
n=14 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Immediate-Release Hydrocortisone
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
|---|---|---|---|
|
Bioavailability of Chronocort® vs Hydrocortisone Tablets - Cmax
|
708.45 nmol/L
Geometric Coefficient of Variation 19.3
|
856.36 nmol/L
Geometric Coefficient of Variation 14.6
|
549.49 nmol/L
Geometric Coefficient of Variation 17.4
|
PRIMARY outcome
Timeframe: 24 hoursPopulation: PK population: All randomised subjects who had sufficient plasma concentration by time profiles for 2 adequate treatments and who did not violate the protocol in such a way that could invalidate or bias the results (major protocol violators).
To evaluate the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state using area under the curve
Outcome measures
| Measure |
Chronocort Fed
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs and subsequently fast overnight. On the morning of Day 1, volunteers will eat a high fat breakfast and take 20mg of randomised treatment with 200 millilitres of water. Water will be allowed 1hr after the study drug is administered. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Chronocort Fasted
n=14 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Immediate-Release Hydrocortisone
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
|---|---|---|---|
|
Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using AUC0-t
|
2980.85 h*nmol/L
Geometric Coefficient of Variation 14.3
|
2466.90 h*nmol/L
Geometric Coefficient of Variation 17.1
|
3229.26 h*nmol/L
Geometric Coefficient of Variation 15.1
|
PRIMARY outcome
Timeframe: 24 hoursPopulation: PK population: All randomised subjects who had sufficient plasma concentration by time profiles for 2 adequate treatments and who did not violate the protocol in such a way that could invalidate or bias the results (major protocol violators).
To evaluate the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state using Tmax.
Outcome measures
| Measure |
Chronocort Fed
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs and subsequently fast overnight. On the morning of Day 1, volunteers will eat a high fat breakfast and take 20mg of randomised treatment with 200 millilitres of water. Water will be allowed 1hr after the study drug is administered. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Chronocort Fasted
n=14 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
Immediate-Release Hydrocortisone
n=18 Participants
Volunteers will be admitted, take dexamethasone to suppress endogenous cortisone at 22.00hrs, fast overnight, and take 20mg of randomised treatment with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
|
|---|---|---|---|
|
Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using Tmax.
|
4.5 hours
Standard Deviation 1.25
|
0.87 hours
Standard Deviation 0.81
|
6.75 hours
Standard Deviation 3.62
|
Adverse Events
Chronocort : Fed
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Chronocort: Fasted
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Immediate Release Hydrocortisone: Fasted
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Chronocort : Fed
n=18 participants at risk
Volunteers will be admitted, take dexamethasone at 22.00hrs, fast overnight, and receive a high fat, high calorie breakfast on the morning of Day 1. Thirty minutes after the start of the breakfast they will receive 20mg of modified release hydrocortisone with 200 millilitres of water, and no further food for 4 hours, water will be allowed from 1 hour after the food. One baseline pharmacokinetics (PK) sample will be taken starting prior to the dose and then over 24 hours (29 samples).
Dexamethasone: Dexamethasone used to suppress endogenous cortisol secretion
Chronocort: fed: single dose of 20mg modified release hydrocortisone in the presence of food
|
Chronocort: Fasted
n=18 participants at risk
Volunteers will be admitted, take dexamethasone at 22.00hrs, fast overnight, and take 20mg modified release hydrocortisone with 200millilitres of water on the morning of Day 1. Water will be allowed 1hr after the dose, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
Dexamethasone: Dexamethasone used to suppress endogenous cortisol secretion
Chronocort: fasted: single dose of 20mg modified release hydrocortisone in the absence of food
|
Immediate Release Hydrocortisone: Fasted
n=17 participants at risk
Volunteers will be admitted, take dexamethasone at 22.00hrs, fast overnight, and take 20mg immediate release hydrocortisone with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)
Dexamethasone: Dexamethasone used to suppress endogenous cortisol secretion
Immediate release hydrocortisone: fasted: single dose of 20mg immediate release hydrocortisone in the absence of food
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.6%
1/18 • Number of events 1 • Each study period is 1.5 days duration, so a total of 4.5 days plus a 7-day washout period between doses
|
0.00%
0/18 • Each study period is 1.5 days duration, so a total of 4.5 days plus a 7-day washout period between doses
|
0.00%
0/17 • Each study period is 1.5 days duration, so a total of 4.5 days plus a 7-day washout period between doses
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.6%
1/18 • Number of events 1 • Each study period is 1.5 days duration, so a total of 4.5 days plus a 7-day washout period between doses
|
0.00%
0/18 • Each study period is 1.5 days duration, so a total of 4.5 days plus a 7-day washout period between doses
|
0.00%
0/17 • Each study period is 1.5 days duration, so a total of 4.5 days plus a 7-day washout period between doses
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place