HealthyPhase 1NCT02408068
Effect of Slow Release Hydrocortisone on Fed & Fasting Volunteers; Immediate Release on Fasting Only
A Phase 1 study testing Dexamethasone, Chronocort: fasted and Immediate release hydrocortisone: fasted in people with Healthy, run by Neurocrine UK Limited.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Dexamethasone, Chronocort: fasted and Immediate release hydrocortisone: fasted
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- Jan 2015to Mar 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
Show all 13Show fewer
- 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:
- Oral contraceptive + condom
- Intra-uterine device + condom
- Diaphragm with spermicide + condom
- Subjects must be available to complete the study
- Subjects must provide written informed consent to participate in the study
Who cannot join
- A clinically significant history of gastrointestinal disorder likely to influence drug absorption
- Receipt of regular medication (including high dose vitamins, dietary supplements or herbal remedies)
- Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction Receipt of any vaccination within the previous one month
- Presence of clinically significant infections (systemic fungal and viral infections, acute bacterial infections)
- Current of previous history of tuberculosis
- A clinically significant history of previous allergy/sensitivity to hydrocortisone and/or dexamethasone
Show all 14Show fewer
- A clinically significant history of family history of psychiatric disorders/illnesses
- A clinically significant history of drug or alcohol abuse
- Inability to communicate well with the investigator (ie language problem, poor mental development or impaired cerebral function)
- Participation in a New Chemical entity clinical study within the previous four months or a marketed drug clinical study within the previous three months
- Subjects who have consumed more than two units of alcohol pre day within seven days prior to the first dose or have consumed any alcohol within the 48hr period prior to the first dose
- Donation of greater than or equal to 450ml blood within the previous three months
- Subjects who smoke or ex-smokers who have smoked within six months prior to first dose
- Subjects who work shifts (ie regularly alternate between days, afternoons and nights)
About this study
Official title: Open Label Randomised 3 Period Crossover Study to Evaluate Bioavailability of Modified Release Hydrocortisone (HC) Under Fasting & Fed Conditions & Immediate Release HC Tablets Under Fasting Conditions in Dexamethasone-suppressed Subjects
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.
Read the detailed description
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.
- Conditions
- Healthy
- Being tested
- Dexamethasone, Chronocort: fasted, Immediate release hydrocortisone: fasted, Chronocort: fed
- Keywords
- subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Dexamethasone used to suppress endogenous cortisol secretion
Chronocort: fastedDrug
Also called modified release hydrocortisone
single dose of 20mg modified release hydrocortisone in the absence of food
Immediate release hydrocortisone: fastedDrug
Also called Hydrocortisone
single dose of 20mg immediate release hydrocortisone in the absence of food
Chronocort: fedDrug
Also called modified release hydrocortisone
single dose of 20mg modified release hydrocortisone in the presence of food
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Dexamethasone; Drug: Chronocort: fed |
| 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) Receives: Drug: Dexamethasone; Drug: Immediate release hydrocortisone: fasted |
| 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) Receives: Drug: Dexamethasone; Drug: Chronocort: fasted |
What is being measured
The primary outcome is the main question the study is designed to answer.
Chronocort Cmax
Comparison of fed and fasted Chronocort Cmax for serum cortisol.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 24 hours
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.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2015 (estimated)
- Study startJan 2015
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurocrine UK Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Simbec Research
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02408068
- Sponsor's protocol ID
- DIUR-004
- Status last verified
- Apr 2022
- First submitted
- 10 Mar 2015
- Last updated
- 4 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Randomised 3 Period Crossover Study to Evaluate Bioavailability of Modified Release Hydrocortisone (HC) Under Fasting & Fed Conditions & Immediate Release HC Tablets Under Fasting Conditions in Dexamethasone-suppressed Subjects
- ClinicalTrials.gov ID
- NCT02408068
- Acronym / sponsor ID
- DIUR-004
- Conditions
- Healthy
- Keywords
- subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Neurocrine UK LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Simbec Research
- Study start
- Jan 2015
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 3 Apr 2015 (estimated)
- Results
- Posted 15 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Chronocort : fed | Active comparator | Drug: Dexamethasone, Drug: Chronocort: fedVolunteers 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 | Drug: Dexamethasone, Drug: Immediate release hydrocortisone: fastedVolunteers 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 | Drug: Dexamethasone, Drug: Chronocort: fastedVolunteers 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) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (14 listed)
- A clinically significant history of gastrointestinal disorder likely to influence drug absorption
- Receipt of regular medication (including high dose vitamins, dietary supplements or herbal remedies)
- Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction Receipt of any vaccination within the previous one month
- Presence of clinically significant infections (systemic fungal and viral infections, acute bacterial infections)
- Current of previous history of tuberculosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneDexamethasone used to suppress endogenous cortisol secretion | Drug | Chronocort : fed, Chronocort: fasted, Immediate release hydrocortisone: fasted |
| Chronocort: fastedAlso: modified release hydrocortisonesingle dose of 20mg modified release hydrocortisone in the absence of food | Drug | Chronocort: fasted |
| Immediate release hydrocortisone: fastedAlso: Hydrocortisonesingle dose of 20mg immediate release hydrocortisone in the absence of food | Drug | Immediate release hydrocortisone: fasted |
| Chronocort: fedAlso: modified release hydrocortisonesingle dose of 20mg modified release hydrocortisone in the presence of food | Drug | Chronocort : fed |
Primary outcome
Chronocort Cmax
Time frame: 24 hours
Comparison of fed and fasted Chronocort Cmax for serum cortisol.
Comparison of Fed and Fasted Chronocort AUC0-t
Time frame: 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.)
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.
Comparison of Fed and Fasted Chronocort Tmax
Time frame: 24 hours
Comparison of Fed and Fasted Chronocort based on the time to achive the maximum concentration of serum cortisol
Bioavailability of Chronocort® vs Hydrocortisone Tablets - Cmax
Time frame: 24 hours
Evaluation of the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state by Cmax
Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using AUC0-t
Time frame: 24 hours
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
Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using Tmax.
Time frame: 24 hours
To evaluate the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state using Tmax.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dexamethasone, Chronocort: fasted and Immediate release hydrocortisone: fasted in people with Healthy, run by Neurocrine UK Limited.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Chronocort Cmax (time frame: 24 hours). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2022.