Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH

• Sponsor: Diurnal Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01735617
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 12
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endocrine Disease; Adrenal Insufficiency; Congenital Adrenal Hyperplasia	Drug: Hydrocortisone Modified Release Capsules	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Pilot Study to Characterize and Examine the Pharmacokinetics and Disease Bio-marker Response of Chronocort® in Adults With Congenital Adrenal Hyperplasia
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: 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; Other Names: Chronocort

Outcome Measures

Primary Outcome Measures

1. 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

2. 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)

3. 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 Outcome Measures

1. 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

2. 17-OHP Levels at 0700h, 1700h and 2300h [Specified time points (0700h, 1700h and 2300h)]

   17-OHP levels at 0700h, 1700h and 2300h

3. Androstenedione Levels at 0700h, 1700h and 2300h [Specified time points (0700h, 1700h and 2300h)]

   Androstenedione levels at 0700h, 1700h and 2300h

4. ACTH Levels at 0700h, 1700h and 2300h [Specified time points (0700h, 1700h and 2300h)]

   ACTH levels at 0700h, 1700h and 2300h

5. 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

6. 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

7. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892-1932

Sponsors and Collaborators

• Diurnal Limited
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Deborah P Merke, BS, MS, MD, National Institutes of Health Clinical Center (CC)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Diurnal Limited
• ClinicalTrials.gov Identifier: NCT01735617
• Other Study ID Numbers: DIUR-003
• First Posted: Nov 28, 2012
• Last Update Posted: May 17, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Diurnal Limited: congenital adrenal hyperplasia; glucocorticoids; cortisol; adrenal
• Additional relevant MeSH terms: Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenal Insufficiency; Adrenocortical Hyperfunction; Endocrine System Diseases; Hyperplasia; Hydrocortisone

Study Results

Participant Flow

Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
Period Title: Overall Study
STARTED	16
COMPLETED	16
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.7 (12.97)
Sex: Female, Male (Count of Participants)
Female	8 50%
Male	8 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 6.3%
White	13 81.3%
More than one race	1 6.3%
Unknown or Not Reported	1 6.3%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia
Description	The maximum plasma concentration (Cmax) of chronocort
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

All treated subjects

Arm/Group Title	Chronocort
Arm/Group Description	Chronocort Modified Release Capsules 10 mg twice-daily.
Measure Participants	16
Mean (Standard Deviation) [nmol/L]	601.213 (114.5987)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chronocort
	Comments	The pharmacokinetic profile was characterised by an overnight rise in cortisol levels reaching a maximal concentration approximately 8 hours post dosing.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric means
	Estimated Value	563.38
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 162.51
	Estimation Comments

2. Primary Outcome

Title	Pharmacokinetic Profile (AUC0-24) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia
Description	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)

Outcome Measure Data

Analysis Population Description

All treated subjects

Arm/Group Title	Chroncort
Arm/Group Description	Chronocort Modified Release Capsules 10mg twice-daily
Measure Participants	16
Mean (Standard Deviation) [h*nmol/L]	5027.641 (1247.8425)

3. Primary Outcome

Title	Pharmacokinetic Profile (Tmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia
Description	Time to maximum plasma concentration (tmax)
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

All treated subjects

Arm/Group Title	Chronocort
Arm/Group Description	Chronocort Modified Release Capsules 10mg twice-daily
Measure Participants	16
Mean (Standard Deviation) [Hours]	7.9 (2.9)

4. Secondary Outcome

Title	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)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
Measure Participants	16
17-OHP (baseline)	0 0%
17-OHP (final visit)	12.5 78.1%
Androstenedione (baseline)	56.3 351.9%
Androstenedione (final visit)	81.3 508.1%

5. Secondary Outcome

Title	17-OHP Levels at 0700h, 1700h and 2300h
Description	17-OHP levels at 0700h, 1700h and 2300h
Time Frame	Specified time points (0700h, 1700h and 2300h)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
Measure Participants	16
17-OHP: Part A, Days 1-2 (0700h)	76.97 (91.986)
17-OHP: Part A, Days 1-2 (1700h)	70.99 (104.106)
17-OHP: Part A, Days 1-2 (2300h)	55.35 (93.632)
17-OHP: Part A, Days 4-5 (0700h)	7.72 (8.231)
17-OHP: Part A, Days 4-5 (1700h)	23.55 (66.046)
17-OHP: Part A, Days 4-5 (2300h)	27.27 (55.140)
17-OHP: Part B, Visit 2 (0700h)	24.86 (54.086)
17-OHP: Part B, Visit 2 (1700h)	15.17 (20.400)
17-OHP: Part B, Visit 2 (2300h)	26.65 (51.185)
17-OHP: Part B, Visit 3 (0700h)	34.87 (49.072)
17-OHP: Part B, Visit 3 (1700h)	13.81 (20.700)
17-OHP: Part B, Visit 3 (2300h)	18.95 (28.276)
17-OHP: Part B, Visit 4 (0700h)	13.67 (19.091)
17-OHP: Part B, Visit 4 (1700h)	34.70 (69.876)
17-OHP: Part B, Visit 4 (2300h)	22.19 (46.826)

6. Secondary Outcome

Title	Androstenedione Levels at 0700h, 1700h and 2300h
Description	Androstenedione levels at 0700h, 1700h and 2300h
Time Frame	Specified time points (0700h, 1700h and 2300h)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
Measure Participants	16
Androstenedione: Part A, Days 1-2 (0700h)	7.92 (8.474)
Androstenedione: Part A, Days 1-2 (1700h)	7.54 (7.966)
Androstenedione: Part A, Days 1-2 (2300h)	7.43 (9.388)
Androstenedione: Part A, Days 4-5 (0700h)	3.11 (2.178)
Androstenedione: Part A, Days 4-5 (1700h)	4.62 (8.005)
Androstenedione: Part A, Days 4-5 (2300h)	5.37 (8.340)
Androstenedione: Part B, Visit 2 (0700h)	4.96 (6.731)
Androstenedione: Part B, Visit 2 (1700h)	3.47 (3.094)
Androstenedione: Part B, Visit 2 (2300h)	3.79 (3.748)
Androstenedione: Part B, Visit 3 (0700h)	4.57 (3.561)
Androstenedione: Part B, Visit 3 (1700h)	3.61 (2.713)
Androstenedione: Part B, Visit 3 (2300h)	3.91 (3.103)
Androstenedione: Part B, Visit 4 (0700h)	3.40 (1.973)
Androstenedione: Part B, Visit 4 (1700h)	4.19 (4.602)
Androstenedione: Part B, Visit 4 (2300h)	3.37 (2.655)

7. Secondary Outcome

Title	ACTH Levels at 0700h, 1700h and 2300h
Description	ACTH levels at 0700h, 1700h and 2300h
Time Frame	Specified time points (0700h, 1700h and 2300h)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
Measure Participants	16
ACTH: Part A, Days 1-2 (0700h)	21.06 (29.767)
ACTH: Part A, Days 1-2 (1700h)	20.93 (30.121)
ACTH: Part A, Days 1-2 (2300h)	7.75 (9.873)
ACTH: Part A, Days 4-5 (0700h)	4.16 (9.190)
ACTH: Part A, Days 4-5 (1700h)	4.71 (7.382)
ACTH: Part A, Days 4-5 (2300h)	7.37 (7.990)
ACTH: Part B, Visit 2 (0700h)	7.02 (12.159)
ACTH: Part B, Visit 2 (1700h)	5.57 (6.769)
ACTH: Part B, Visit 2 (2300h)	8.66 (14.637)
ACTH: Part B, Visit 3 (0700h)	9.66 (12.418)
ACTH: Part B, Visit 3 (1700h)	4.71 (6.331)
ACTH: Part B, Visit 3 (2300h)	6.04 (7.997)
ACTH: Part B, Visit 4 (0700h)	12.18 (29.911)
ACTH: Part B, Visit 4 (1700h)	13.66 (22.851)
ACTH: Part B, Visit 4 (2300h)	9.44 (17.474)

8. Secondary Outcome

Title	AUC Values (Nmol*h/L) for Androstenedione
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
Measure Participants	16
Androstenedione: Part A, Days 1-2 AUC (2300-2300h)	166.19 (171.969)
Androstenedione: Part A, Days 1-2 AUC (2300-0700h)	41.42 (34.133)
Androstenedione: Part A, Days 1-2 AUC (0700-1500h)	65.33 (76.337)
Androstenedione: Part A, Days 1-2 AUC (1500-2300h)	59.44 (65.995)
Androstenedione: Part A, Days 4-5 AUC (2300-2300h)	104.37 (128.725)
Androstenedione: Part A, Days 4-5 AUC (2300-0700h)	36.02 (40.225)
Androstenedione: Part A, Days 4-5 AUC (0700-1500h)	32.01 (31.503)
Androstenedione: Part A, Days 4-5 AUC (1500-2300h)	37.91 (58.394)
Androstenedione: Part B, Visit 2 AUC (2300-2300h)	88.58 (86.364)
Androstenedione: Part B, Visit 2 AUC (2300-0700h)	35.12 (43.580)
Androstenedione: Part B, Visit 2 AUC (0700-1500h)	26.07 (22.298)
Androstenedione: Part B, Visit 2 AUC (1500-2300h)	27.39 (23.989)
Androstenedione: Part B, Visit 3 AUC (2300-2300h)	91.46 (65.295)
Androstenedione: Part B, Visit 3 AUC (2300-0700h)	33.25 (26.255)
Androstenedione: Part B, Visit 3 AUC (0700-1500h)	27.92 (16.297)
Androstenedione: Part B, Visit 3 AUC (1500-2300h)	30.30 (26.188)
Androstenedione: Part B, Visit 4 AUC (2300-2300h)	86.27 (70.892)
Androstenedione: Part B, Visit 4 AUC (2300-0700h)	29.09 (23.314)
Androstenedione: Part B, Visit 4 AUC (0700-1500h)	27.03 (20.009)
Androstenedione: Part B, Visit 4 AUC (1500-2300h)	30.13 (28.797)

9. Secondary Outcome

Title	AUC Values (Nmol*h/L) for 17-OHP
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
Measure Participants	16
17-OHP: Part A, Days 1-2 AUC 2300-2300h	1407.83 (1829.291)
17-OHP: Part A, Days 1-2 AUC 2300-0700h	243.99 (339.580)
17-OHP: Part A, Days 1-2 AUC 0700-1500h	607.74 (805.822)
17-OHP: Part A, Days 1-2 AUC 1500-2300h	556.11 (769.492)
17-OHP: Part A, Days 4-5 AUC 2300-2300h	446.90 (817.074)
17-OHP: Part A, Days 4-5 AUC 2300-0700h	169.83 (268.178)
17-OHP: Part A, Days 4-5 AUC 0700-1500h	91.53 (147.801)
17-OHP: Part A, Days 4-5 AUC 1500-2300h	190.73 (425.505)
17-OHP: Part B, Visit 2 AUC 2300-2300h	395.65 (587.533)
17-OHP: Part B, Visit 2 AUC 2300-0700h	168.01 (337.666)
17-OHP: Part B, Visit 2 AUC 0700-1500h	82.41 (91.708)
17-OHP: Part B, Visit 2 AUC 1500-2300h	145.24 (215.115)
17-OHP: Part B, Visit 3 AUC 2300-2300h	432.02 (393.897)
17-OHP: Part B, Visit 3 AUC 2300-0700h	152.63 (144.576)
17-OHP: Part B, Visit 3 AUC 0700-1500h	139.21 (147.353)
17-OHP: Part B, Visit 3 AUC 1500-2300h	140.18 (182.786)
17-OHP: Part B, Visit 4 AUC 2300-2300h	436.54 (678.052)
17-OHP: Part B, Visit 4 AUC 2300-0700h	101.33 (148.003)
17-OHP: Part B, Visit 4 AUC 0700-1500h	120.32 (172.134)
17-OHP: Part B, Visit 4 AUC 1500-2300h	214.89 (364.641)

10. Secondary Outcome

Title	AUC Values (Pmol*h/L) for ACTH
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
Measure Participants	16
ACTH: Part A, Days 1-2 AUC (2300-2300h)	356.25 (415.949)
ACTH: Part A, Days 1-2 AUC (2300-0700h)	54.72 (70.267)
ACTH: Part A, Days 1-2 AUC (0700-1500h)	166.18 (206.294)
ACTH: Part A, Days 1-2 AUC (1500-2300h)	135.35 (169.002)
ACTH: Part A, Days 4-5 AUC (2300-2300h)	120.00 (121.454)
ACTH: Part A, Days 4-5 AUC (2300-0700h)	52.22 (62.067)
ACTH: Part A, Days 4-5 AUC (0700-1500h)	21.29 (19.824)
ACTH: Part A, Days 4-5 AUC (1500-2300h)	47.13 (57.145)
ACTH: Part B, Visit 2 AUC (2300-2300h)	125.45 (118.081)
ACTH: Part B, Visit 2 AUC (2300-0700h)	43.09 (46.711)
ACTH: Part B, Visit 2 AUC (0700-1500h)	34.14 (48.423)
ACTH: Part B, Visit 2 AUC (1500-2300h)	48.22 (49.078)
ACTH: Part B, Visit 3 AUC (2300-2300h)	154.10 (172.474)
ACTH: Part B, Visit 3 AUC (2300-0700h)	50.02 (57.268)
ACTH: Part B, Visit 3 AUC (0700-1500h)	52.46 (64.571)
ACTH: Part B, Visit 3 AUC (1500-2300h)	51.63 (70.735)
ACTH: Part B, Visit 4 AUC (2300-2300h)	252.30 (420.220)
ACTH: Part B, Visit 4 AUC (2300-0700h)	58.80 (107.955)
ACTH: Part B, Visit 4 AUC (0700-1500h)	110.58 (329.386)
ACTH: Part B, Visit 4 AUC (1500-2300h)	82.92 (120.287)

Adverse Events

Time Frame	Approximately 7 months
Arm/Group Title	Hydrocortisone Modified Release Capsules
Arm/Group Description	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
All Cause Mortality
	Hydrocortisone Modified Release Capsules
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Hydrocortisone Modified Release Capsules
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Hydrocortisone Modified Release Capsules
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Blood and lymphatic system disorders
Anaemia	7/16 (43.8%)	9
General disorders
Fatigue	13/16 (81.3%)	13
Asthenia	5/16 (31.3%)	5
Investigations
Weight increase	7/16 (43.8%)	7
Metabolism and nutrition disorders
Appetite decrease	7/16 (43.8%)	7
Appetite increase	6/16 (37.5%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	5/16 (31.3%)	5
Nervous system disorders
Headache	13/16 (81.3%)	13
Dizziness	8/16 (50%)	8
Psychiatric disorders
Insomnia	5/16 (31.3%)	5
Skin and subcutaneous tissue disorders
Acne	5/16 (31.3%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.