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| Name | Class |
|---|---|
| Simbec Research | INDUSTRY |
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The purpose of the study is to find out whether food has an effect on the way the body deals with modified release hydrocortisone, and to compare with the pharmacokinetics of immediate release hydrocortisone (fasted). This information will be used to help doctors with dosing in clinical practice.
This is a phase I study in healthy male volunteers, who will be given dexamethasone to suppress their natural cortisol production. 18 will be consented for the study. They will have had a history and a physical examination, blood tests for routine safety, hepatitis C and Human Immunodeficiency Virus (HIV), drug abuse and Electrocardiograms (ECGs). Following the results of these tests and the inclusion/exclusion criteria for the study, they will be admitted to the phase I unit on the first afternoon (Day -1). They will be given dexamethasone at 22.00hrs that evening, and remain in the unit until the end of the period. Further dexamethasone doses will be given at 06:00, 12:00, and 18:00 hours on Day 1 (plus at 22:00 hours in patients given the modified release study drug). Each volunteer will be admitted for 3 periods of approximately 1.5 days, with a washout of 7 days between periods, and they will be randomised to either fast and take a single 20mg dose of immediate release hydrocortisone, to fast and take a single 20mg dose of the study medication, (a modified release hydrocortisone), or to the "fed" group, where they take a single dose of 20mg study medication, and have a highly calorific standardised breakfast. The volunteers will have cannulae to enable one pre-dose blood sample to be taken followed by 24 hour Pharmacokinetic (PK) sampling (modified release) and 12 hour PK sampling for the immediate release period. After these samples have been taken the volunteers will be able to leave the unit. There will be another assessment 3 to 5 days after study period 3 with further blood tests, assessment of any adverse events etc.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronocort : fed | Active Comparator | 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. Further dexamethasone doses will be given at 06:00, 12:00, 18:00 and 22:00 hours on Day 1. One baseline pharmacokinetics (PK) sample will be taken starting prior to the dose and then over 24 hours (29 samples). |
|
| Immediate release hydrocortisone: fasted | Active Comparator | 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. Further dexamethasone doses will be given at 06:00, 12:00 and 18:00 hours on Day 1. 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 | Active Comparator | 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. Further dexamethasone doses will be given at 06:00, 12:00, 18:00 and 22:00 hours on Day 1. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexamethasone | Drug | Dexamethasone used to suppress endogenous cortisol secretion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Chronocort Cmax | Comparison of fed and fasted Chronocort Cmax for serum cortisol. | 24 hours |
| Comparison of Fed and Fasted Chronocort AUC0-t | 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. | 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.) |
| Comparison of Fed and Fasted Chronocort Tmax | Comparison of Fed and Fasted Chronocort based on the time to achive the maximum concentration of serum cortisol | 24 hours |
| Bioavailability of Chronocort® vs Hydrocortisone Tablets - Cmax | Evaluation of the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state by Cmax | 24 hours |
| Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using AUC0-t | 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 | 24 hours |
| Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using Tmax. |
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Inclusion Criteria:
Healthy male volunteers between 18 and 60 years of age, inclusive (at screening)
A body mass index of 21-28 (inclusive).
No clinically significant abnormal serum biochemistry, haematology and urine examination values
A negative urinary drugs of abuse screen. A positive alcohol test may be repeated at the discretion of the investigator.
Negative Human Immunodeficiency Virus (HIV) and Hepatitis b & C results
No clinically significant abnormalities in 12-lead Electrocardiogram (ECG)
No clinically significant deviation outside the normal ranges for blood pressure and pulse measurements
Subjects (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) and sexual partners must use effective contraception methods during the trial and for 3 months after the last dose, for example:
Subjects must be available to complete the study
Subjects must provide written informed consent to participate in the study
Exclusion Criteria:
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 | Chronocort 20mg (fed), Chronocort 20mg (fasted), Hydrocortisone 20mg (fasted) |
| FG001 | Sequence 2 | Chronocort 20mg (fed), Hydrocortisone 20mg (fasted), Chronocort 20mg (fasted) |
| FG002 | Sequence 3 | Chronocort 20mg (fasted), Chronocort 20mg (fed), Hydrocortisone 20mg (fasted) |
| FG003 | Sequence 4 | Chronocort 20mg (fasted), Hydrocortisone 20mg (fasted), Chronocort 20mg (fed) |
| FG004 | Sequence 5 | Hydrocortisone 20mg (fasted), Chronocort 20mg (fed), Chronocort 20mg (fasted) |
| FG005 | Sequence 6 | Hydrocortisone 20mg (fasted), Chronocort 20mg (fasted), Chronocort 20mg (fed) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment 1 (1.5 Days) |
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| Washout Period 1 (7 Days) |
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| Treatment 2 (1.5 Days) |
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| Washout Period 2 (7 Days) |
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| Treatment 3 (1.5 Days) |
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Cross-over study so all patients received all treatments
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | All patients received all 3 study treatments in randomised order |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Chronocort Cmax | Comparison of fed and fasted Chronocort Cmax for serum cortisol. | 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). | Posted | Geometric Least Squares Mean | Geometric Coefficient of Variation | nmol/L | 24 hours |
|
Each study period is 1.5 days duration, so a total of 4.5 days plus a 7-day washout period between doses
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Chronocort : Fed | 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr G Sharma | Simbec Research Ltd | 0800 691995 | contact@simbec.com |
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| ID | Term |
|---|---|
| D003907 | Dexamethasone |
| D006854 | Hydrocortisone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
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| Chronocort: fasted | Drug | single dose of 20mg modified release hydrocortisone in the absence of food |
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| Immediate release hydrocortisone: fasted | Drug | single dose of 20mg immediate release hydrocortisone in the absence of food |
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| Chronocort: fed | Drug | single dose of 20mg modified release hydrocortisone in the presence of food |
|
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To evaluate the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state using Tmax.
| 24 hours |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG001 | Chronocort Fasted | 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) |
| OG002 | Immediate-Release Hydrocortisone | 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) |
|
|
|
| Primary | Comparison of Fed and Fasted Chronocort AUC0-t | 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. | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | 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.) |
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| Primary | Comparison of Fed and Fasted Chronocort Tmax | Comparison of Fed and Fasted Chronocort based on the time to achive the maximum concentration of serum cortisol | 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). | Posted | Median | Standard Deviation | hours | 24 hours |
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|
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| Primary | Bioavailability of Chronocort® vs Hydrocortisone Tablets - Cmax | Evaluation of the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state by Cmax | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol/L | 24 hours |
|
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| Primary | Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using AUC0-t | 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 | 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). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*nmol/L | 24 hours |
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| Primary | Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using Tmax. | To evaluate the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state using Tmax. | 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). | Posted | Median | Standard Deviation | hours | 24 hours |
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| 0 |
| 18 |
| 1 |
| 18 |
| EG001 | Chronocort: Fasted | 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 | 0 | 18 | 0 | 18 |
| EG002 | Immediate Release Hydrocortisone: Fasted | 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 | 0 | 17 | 0 | 17 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
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| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D015062 | 11-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D015065 | 17-Hydroxycorticosteroids |