Adrenal Insufficiency, Congenital Adrenal Hyperplasia, Endocrine Disease
Conditions
Keywords
congenital adrenal hyperplasia, glucocorticoids, cortisol, adrenal
Brief summary
The purpose of this study is to gather safety and effectiveness information about a new formulation of Hydrocortisone (Chronocort®) used to treat patients with a disease called congenital adrenal hyperplasia (CAH). Hydrocortisone is the man-made version of the hormone cortisol, which is released in the body following a regular daily pattern. The objective of the study is to measure the levels of hydrocortisone that are absorbed into the bloodstream once Chronocort® is taken and what affects it has on other hormones in the body. Since Chronocort® is anticipated to mimic the same release pattern of cortisol in the body, it is hoped that patients with CAH will be treated more effectively to manage their disease.
Detailed description
This study is a Phase 2 pilot study to characterize and examine the pharmacokinetics and efficacy profile of Chronocort® in adults with congenital adrenal hyperplasia (CAH). It is designed as a two-part, single cohort, open label, multiple dose Phase 2 pilot study to: (Part A) characterize and examine the pharmacokinetics (PK) and disease bio-marker behavior following short-term dosing with Chronocort®; and to (Part B) examine the disease control after six months dose titration with Chronocort® in adults with CAH.
Interventions
DRUGHydrocortisone Modified Release Capsules
Patients with congenital adrenal hyperplasia standardised on conventional therapy is enrolled onto the study and treatment is switched to Chronocort, initially for pharmacokinetic assessment followed by longer-term biochemical and efficacy assessment
Sponsors
National Institutes of Health (NIH)
Neurocrine UK Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Known CAH due to 21-hydroxylase deficiency (classic CAH) based on hormonal and genetic testing currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone on a stable dosage for a minimum of 3 months. 2. Male or female patients aged 18 and above. 3. Provision of signed written informed consent. 4. Good general health. 5. Females of childbearing potential must have a negative pregnancy test initially and at all visits. Females who are engaging in sexual intercourse must be using a medically acceptable method of contraception (as defined in the protocol, section 10.5). 6. Plasma renin activity must be within the clinically acceptable range at screening (less than 1.5 times upper normal range).
Exclusion criteria
1. Co-morbid condition requiring daily administration of a medication that induces hepatic enzymes or interferes with the metabolism of glucocorticoids. 2. Clinical or biochemical evidence of hepatic or renal disease. Creatinine above the normal range or elevated liver function tests (ALT or AST) \> 2 times the upper limits of normal. 3. Females who are pregnant or lactating. 4. Women taking an estrogen-containing oral contraceptive pill and who have taken it within 6 weeks of recruitment. 5. Patients taking spironolactone. 6. Patients on inhaled or oral steroids apart from treatment for CAH. 7. Patients with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the trial. 8. Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study. 9. Patients with history of bilateral adrenalectomy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia | 24 hours | The maximum plasma concentration (Cmax) of chronocort |
| Pharmacokinetic Profile (AUC0-24) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia | 24 hours (at 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs) | Area under the curve (AUC) from 0 to 24 hours (sampling occurs at the following timepoints: 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs) |
| Pharmacokinetic Profile (Tmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia | 24 hours | Time to maximum plasma concentration (tmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ACTH Levels at 0700h, 1700h and 2300h | Specified time points (0700h, 1700h and 2300h) | ACTH levels at 0700h, 1700h and 2300h |
| AUC Values (Nmol*h/L) for Androstenedione | Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h) | AUC values (nmol\*h/L) for Androstenedione for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h |
| The Percentage of Patients With 17-OHP and Androstenedione Levels at 0700h Within Proposed Optimal Ranges Whilst on Chronocort and Whilst on Standard Therapy (at Baseline) | Specific time point (0700hrs) | Proposed optimal ranges of 17-OHP: 300-1200ng/dl Proposed optimal ranges of androstenedione: 40-150ng.dl for males and 30-200ng/dl for females |
| AUC Values (Pmol*h/L) for ACTH | Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h) | AUC values (pmol\*h/L) for ACTH for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h |
| AUC Values (Nmol*h/L) for 17-OHP | Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h) | AUC values (nmol\*h/L) for 17-OHP for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h |
| 17-OHP Levels at 0700h, 1700h and 2300h | Specified time points (0700h, 1700h and 2300h) | 17-OHP levels at 0700h, 1700h and 2300h |
| Androstenedione Levels at 0700h, 1700h and 2300h | Specified time points (0700h, 1700h and 2300h) | Androstenedione levels at 0700h, 1700h and 2300h |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydrocortisone Modified Release Capsules Chronocort Modified Release Capsules, 5mg, 10mg and 20mg Dosing frequency twice-daily (mane and nocte) Dose setting by titration to achieve optimal biochemical and therapeutic response
Hydrocortisone Modified Release Capsules: Patients with congenital adrenal hyperplasia standardised on conventional therapy is enrolled onto the study and treatment is switched to Chronocort, initially for pharmacokinetic assessment followed by longer-term biochemical and efficacy assessment | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Hydrocortisone Modified Release Capsules |
|---|---|
| Age, Continuous | 28.7 years STANDARD_DEVIATION 12.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Pharmacokinetic Profile (AUC0-24) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia
Area under the curve (AUC) from 0 to 24 hours (sampling occurs at the following timepoints: 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs)
Time frame: 24 hours (at 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs)
Population: All treated subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort | Pharmacokinetic Profile (AUC0-24) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia | 5027.641 h*nmol/L | Standard Deviation 1247.8425 |
Primary
Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia
The maximum plasma concentration (Cmax) of chronocort
Time frame: 24 hours
Population: All treated subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort | Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia | 601.213 nmol/L | Standard Deviation 114.5987 |
Comparison: The pharmacokinetic profile was characterised by an overnight rise in cortisol levels reaching a maximal concentration approximately 8 hours post dosing.
Primary
Pharmacokinetic Profile (Tmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia
Time to maximum plasma concentration (tmax)
Time frame: 24 hours
Population: All treated subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronocort | Pharmacokinetic Profile (Tmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia | 7.9 Hours | Standard Deviation 2.9 |
Secondary
17-OHP Levels at 0700h, 1700h and 2300h
17-OHP levels at 0700h, 1700h and 2300h
Time frame: Specified time points (0700h, 1700h and 2300h)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part A, Days 1-2 (0700h) | 76.97 nmol/L | Standard Deviation 91.986 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part A, Days 1-2 (1700h) | 70.99 nmol/L | Standard Deviation 104.106 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part A, Days 1-2 (2300h) | 55.35 nmol/L | Standard Deviation 93.632 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part A, Days 4-5 (0700h) | 7.72 nmol/L | Standard Deviation 8.231 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part A, Days 4-5 (1700h) | 23.55 nmol/L | Standard Deviation 66.046 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part A, Days 4-5 (2300h) | 27.27 nmol/L | Standard Deviation 55.14 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part B, Visit 2 (0700h) | 24.86 nmol/L | Standard Deviation 54.086 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part B, Visit 2 (1700h) | 15.17 nmol/L | Standard Deviation 20.4 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part B, Visit 2 (2300h) | 26.65 nmol/L | Standard Deviation 51.185 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part B, Visit 3 (0700h) | 34.87 nmol/L | Standard Deviation 49.072 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part B, Visit 3 (1700h) | 13.81 nmol/L | Standard Deviation 20.7 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part B, Visit 3 (2300h) | 18.95 nmol/L | Standard Deviation 28.276 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part B, Visit 4 (0700h) | 13.67 nmol/L | Standard Deviation 19.091 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part B, Visit 4 (1700h) | 34.70 nmol/L | Standard Deviation 69.876 |
| Chronocort | 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP: Part B, Visit 4 (2300h) | 22.19 nmol/L | Standard Deviation 46.826 |
Secondary
ACTH Levels at 0700h, 1700h and 2300h
ACTH levels at 0700h, 1700h and 2300h
Time frame: Specified time points (0700h, 1700h and 2300h)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part A, Days 1-2 (0700h) | 21.06 pmol/L | Standard Deviation 29.767 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part A, Days 1-2 (1700h) | 20.93 pmol/L | Standard Deviation 30.121 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part A, Days 1-2 (2300h) | 7.75 pmol/L | Standard Deviation 9.873 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part A, Days 4-5 (0700h) | 4.16 pmol/L | Standard Deviation 9.19 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part A, Days 4-5 (1700h) | 4.71 pmol/L | Standard Deviation 7.382 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part A, Days 4-5 (2300h) | 7.37 pmol/L | Standard Deviation 7.99 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part B, Visit 2 (0700h) | 7.02 pmol/L | Standard Deviation 12.159 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part B, Visit 2 (1700h) | 5.57 pmol/L | Standard Deviation 6.769 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part B, Visit 2 (2300h) | 8.66 pmol/L | Standard Deviation 14.637 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part B, Visit 3 (0700h) | 9.66 pmol/L | Standard Deviation 12.418 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part B, Visit 3 (1700h) | 4.71 pmol/L | Standard Deviation 6.331 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part B, Visit 3 (2300h) | 6.04 pmol/L | Standard Deviation 7.997 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part B, Visit 4 (0700h) | 12.18 pmol/L | Standard Deviation 29.911 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part B, Visit 4 (1700h) | 13.66 pmol/L | Standard Deviation 22.851 |
| Chronocort | ACTH Levels at 0700h, 1700h and 2300h | ACTH: Part B, Visit 4 (2300h) | 9.44 pmol/L | Standard Deviation 17.474 |
Secondary
Androstenedione Levels at 0700h, 1700h and 2300h
Androstenedione levels at 0700h, 1700h and 2300h
Time frame: Specified time points (0700h, 1700h and 2300h)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part A, Days 1-2 (0700h) | 7.92 nmol/L | Standard Deviation 8.474 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part A, Days 1-2 (1700h) | 7.54 nmol/L | Standard Deviation 7.966 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part A, Days 1-2 (2300h) | 7.43 nmol/L | Standard Deviation 9.388 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part A, Days 4-5 (0700h) | 3.11 nmol/L | Standard Deviation 2.178 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part A, Days 4-5 (1700h) | 4.62 nmol/L | Standard Deviation 8.005 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part B, Visit 4 (0700h) | 3.40 nmol/L | Standard Deviation 1.973 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part A, Days 4-5 (2300h) | 5.37 nmol/L | Standard Deviation 8.34 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part B, Visit 2 (0700h) | 4.96 nmol/L | Standard Deviation 6.731 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part B, Visit 2 (1700h) | 3.47 nmol/L | Standard Deviation 3.094 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part B, Visit 2 (2300h) | 3.79 nmol/L | Standard Deviation 3.748 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part B, Visit 3 (0700h) | 4.57 nmol/L | Standard Deviation 3.561 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part B, Visit 3 (1700h) | 3.61 nmol/L | Standard Deviation 2.713 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part B, Visit 3 (2300h) | 3.91 nmol/L | Standard Deviation 3.103 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part B, Visit 4 (1700h) | 4.19 nmol/L | Standard Deviation 4.602 |
| Chronocort | Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione: Part B, Visit 4 (2300h) | 3.37 nmol/L | Standard Deviation 2.655 |
Secondary
AUC Values (Nmol*h/L) for 17-OHP
AUC values (nmol\*h/L) for 17-OHP for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h
Time frame: Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 2 AUC 2300-2300h | 395.65 nmol*h/L | Standard Deviation 587.533 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 2 AUC 2300-0700h | 168.01 nmol*h/L | Standard Deviation 337.666 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 2 AUC 0700-1500h | 82.41 nmol*h/L | Standard Deviation 91.708 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 2 AUC 1500-2300h | 145.24 nmol*h/L | Standard Deviation 215.115 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 4 AUC 2300-2300h | 436.54 nmol*h/L | Standard Deviation 678.052 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 4 AUC 2300-0700h | 101.33 nmol*h/L | Standard Deviation 148.003 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part A, Days 1-2 AUC 2300-2300h | 1407.83 nmol*h/L | Standard Deviation 1829.291 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part A, Days 1-2 AUC 2300-0700h | 243.99 nmol*h/L | Standard Deviation 339.58 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part A, Days 1-2 AUC 0700-1500h | 607.74 nmol*h/L | Standard Deviation 805.822 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part A, Days 1-2 AUC 1500-2300h | 556.11 nmol*h/L | Standard Deviation 769.492 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part A, Days 4-5 AUC 2300-2300h | 446.90 nmol*h/L | Standard Deviation 817.074 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part A, Days 4-5 AUC 2300-0700h | 169.83 nmol*h/L | Standard Deviation 268.178 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part A, Days 4-5 AUC 0700-1500h | 91.53 nmol*h/L | Standard Deviation 147.801 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part A, Days 4-5 AUC 1500-2300h | 190.73 nmol*h/L | Standard Deviation 425.505 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 3 AUC 2300-2300h | 432.02 nmol*h/L | Standard Deviation 393.897 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 3 AUC 2300-0700h | 152.63 nmol*h/L | Standard Deviation 144.576 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 3 AUC 0700-1500h | 139.21 nmol*h/L | Standard Deviation 147.353 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 3 AUC 1500-2300h | 140.18 nmol*h/L | Standard Deviation 182.786 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 4 AUC 0700-1500h | 120.32 nmol*h/L | Standard Deviation 172.134 |
| Chronocort | AUC Values (Nmol*h/L) for 17-OHP | 17-OHP: Part B, Visit 4 AUC 1500-2300h | 214.89 nmol*h/L | Standard Deviation 364.641 |
Secondary
AUC Values (Nmol*h/L) for Androstenedione
AUC values (nmol\*h/L) for Androstenedione for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h
Time frame: Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part A, Days 1-2 AUC (1500-2300h) | 59.44 nmol*h/L | Standard Deviation 65.995 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part A, Days 4-5 AUC (2300-2300h) | 104.37 nmol*h/L | Standard Deviation 128.725 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part A, Days 4-5 AUC (2300-0700h) | 36.02 nmol*h/L | Standard Deviation 40.225 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part A, Days 1-2 AUC (2300-2300h) | 166.19 nmol*h/L | Standard Deviation 171.969 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part A, Days 1-2 AUC (2300-0700h) | 41.42 nmol*h/L | Standard Deviation 34.133 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part A, Days 1-2 AUC (0700-1500h) | 65.33 nmol*h/L | Standard Deviation 76.337 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part A, Days 4-5 AUC (0700-1500h) | 32.01 nmol*h/L | Standard Deviation 31.503 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part A, Days 4-5 AUC (1500-2300h) | 37.91 nmol*h/L | Standard Deviation 58.394 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 2 AUC (2300-2300h) | 88.58 nmol*h/L | Standard Deviation 86.364 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 2 AUC (2300-0700h) | 35.12 nmol*h/L | Standard Deviation 43.58 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 2 AUC (0700-1500h) | 26.07 nmol*h/L | Standard Deviation 22.298 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 2 AUC (1500-2300h) | 27.39 nmol*h/L | Standard Deviation 23.989 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 3 AUC (2300-2300h) | 91.46 nmol*h/L | Standard Deviation 65.295 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 3 AUC (2300-0700h) | 33.25 nmol*h/L | Standard Deviation 26.255 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 3 AUC (0700-1500h) | 27.92 nmol*h/L | Standard Deviation 16.297 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 3 AUC (1500-2300h) | 30.30 nmol*h/L | Standard Deviation 26.188 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 4 AUC (2300-2300h) | 86.27 nmol*h/L | Standard Deviation 70.892 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 4 AUC (2300-0700h) | 29.09 nmol*h/L | Standard Deviation 23.314 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 4 AUC (0700-1500h) | 27.03 nmol*h/L | Standard Deviation 20.009 |
| Chronocort | AUC Values (Nmol*h/L) for Androstenedione | Androstenedione: Part B, Visit 4 AUC (1500-2300h) | 30.13 nmol*h/L | Standard Deviation 28.797 |
Secondary
AUC Values (Pmol*h/L) for ACTH
AUC values (pmol\*h/L) for ACTH for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h
Time frame: Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part A, Days 1-2 AUC (2300-2300h) | 356.25 pmol*h/L | Standard Deviation 415.949 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part A, Days 1-2 AUC (2300-0700h) | 54.72 pmol*h/L | Standard Deviation 70.267 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part A, Days 1-2 AUC (0700-1500h) | 166.18 pmol*h/L | Standard Deviation 206.294 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part A, Days 1-2 AUC (1500-2300h) | 135.35 pmol*h/L | Standard Deviation 169.002 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part A, Days 4-5 AUC (2300-2300h) | 120.00 pmol*h/L | Standard Deviation 121.454 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part A, Days 4-5 AUC (2300-0700h) | 52.22 pmol*h/L | Standard Deviation 62.067 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part A, Days 4-5 AUC (0700-1500h) | 21.29 pmol*h/L | Standard Deviation 19.824 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part A, Days 4-5 AUC (1500-2300h) | 47.13 pmol*h/L | Standard Deviation 57.145 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 2 AUC (2300-2300h) | 125.45 pmol*h/L | Standard Deviation 118.081 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 2 AUC (2300-0700h) | 43.09 pmol*h/L | Standard Deviation 46.711 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 2 AUC (0700-1500h) | 34.14 pmol*h/L | Standard Deviation 48.423 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 2 AUC (1500-2300h) | 48.22 pmol*h/L | Standard Deviation 49.078 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 3 AUC (2300-2300h) | 154.10 pmol*h/L | Standard Deviation 172.474 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 3 AUC (2300-0700h) | 50.02 pmol*h/L | Standard Deviation 57.268 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 3 AUC (0700-1500h) | 52.46 pmol*h/L | Standard Deviation 64.571 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 3 AUC (1500-2300h) | 51.63 pmol*h/L | Standard Deviation 70.735 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 4 AUC (2300-2300h) | 252.30 pmol*h/L | Standard Deviation 420.22 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 4 AUC (2300-0700h) | 58.80 pmol*h/L | Standard Deviation 107.955 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 4 AUC (0700-1500h) | 110.58 pmol*h/L | Standard Deviation 329.386 |
| Chronocort | AUC Values (Pmol*h/L) for ACTH | ACTH: Part B, Visit 4 AUC (1500-2300h) | 82.92 pmol*h/L | Standard Deviation 120.287 |
Secondary
The Percentage of Patients With 17-OHP and Androstenedione Levels at 0700h Within Proposed Optimal Ranges Whilst on Chronocort and Whilst on Standard Therapy (at Baseline)
Proposed optimal ranges of 17-OHP: 300-1200ng/dl Proposed optimal ranges of androstenedione: 40-150ng.dl for males and 30-200ng/dl for females
Time frame: Specific time point (0700hrs)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chronocort | The Percentage of Patients With 17-OHP and Androstenedione Levels at 0700h Within Proposed Optimal Ranges Whilst on Chronocort and Whilst on Standard Therapy (at Baseline) | 17-OHP (baseline) | 0 percentage of participants |
| Chronocort | The Percentage of Patients With 17-OHP and Androstenedione Levels at 0700h Within Proposed Optimal Ranges Whilst on Chronocort and Whilst on Standard Therapy (at Baseline) | 17-OHP (final visit) | 12.5 percentage of participants |
| Chronocort | The Percentage of Patients With 17-OHP and Androstenedione Levels at 0700h Within Proposed Optimal Ranges Whilst on Chronocort and Whilst on Standard Therapy (at Baseline) | Androstenedione (baseline) | 56.3 percentage of participants |
| Chronocort | The Percentage of Patients With 17-OHP and Androstenedione Levels at 0700h Within Proposed Optimal Ranges Whilst on Chronocort and Whilst on Standard Therapy (at Baseline) | Androstenedione (final visit) | 81.3 percentage of participants |