CONnECT: Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia
Study Details
Study Description
Brief Summary
This study is a randomized, double-blind, active-controlled, phase III study of Chronocort® compared with immediate-release hydrocortisone replacement therapy in participants aged 16 years and over with Congenital Adrenal Hyperplasia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
The study will compare the efficacy, safety and tolerability of twice daily Chronocort with twice daily immediate release hydrocortisone replacement therapy (IRHC) (Cortef®) over a randomized treatment period of up to 52 weeks in participants aged 16 years and over with known classic Congenital Adrenal Hyperplasia (CAH) due to 21 hydroxylase deficiency. The primary efficacy assessment of biochemical responder rate and the key secondary assessment of dose responder rate will be assessed after 52 weeks of randomized treatment.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Chronocort Hydrocortisone modified-release capsule - Chronocort®. 63 subjects will be randomised to this group using an interactive response technology (IRT). |
Drug: Chronocort
Over-encapsulated hydrocortisone modified-release capsules for oral administration - 5mg and 10mg
Other Names:
|
| Active Comparator: Cortef Immediate-release hydrocortisone capsule (IRHC) - Cortef. 63 subjects will be randomised to this group using an interactive response technology (IRT). |
Drug: Cortef
Over-encapsulated immediate-release hydrocortisone capsules for oral administration - 5mg and 20mg
Other Names:
|
Outcome Measures
Primary Outcome Measures
- To compare Chronocort to IRHC in terms of biochemical responder rate after 52 weeks of randomized treatment - 17-OHP concentration [52 weeks]
Biochemical control defined as a 17-OHP concentration equal to or below the upper limit for optimal control.
- To compare Chronocort to IRHC in terms of biochemical responder rate after 52 weeks of randomized treatment - A4 concentration [52 weeks]
Biochemical control defined as a A4 concentration equal to or below the upper limit for optimal control.
- To compare Chronocort to IRHC in terms of biochemical responder rate after 52 weeks of randomized treatment - Total daily dose of Hydrocortisone [52 weeks]
Biochemical control defined as receiving after 52 weeks of randomized treatment a total daily dose of hydrocortisone of not more than 25 mg (if the participant was in biochemical control at baseline) or not more than 30 mg (if the participant was not in biochemical control at baseline).
Secondary Outcome Measures
- To compare Chronocort to IRHC in terms of dose responder rate after 52 weeks of randomized treatment - Total daily dose [52 weeks]
A dose responder defined as a participant receiving after 52 weeks of randomized treatment a total daily dose of hydrocortisone of not more than 25 mg.
- To compare Chronocort to IRHC in terms of dose responder rate after 52 weeks of randomized treatment - 17-OHP concentration [52 weeks]
A dose responder defined as a participant in biochemical control at the 08:00 hours assessment after 52 weeks of randomized treatment (where in biochemical control is defined as a 17-OHP concentration equal to or below the upper limit for optimal control.
- To compare Chronocort to IRHC in terms of dose responder rate after 52 weeks of randomized treatment - A4 concentration [52 weeks]
A dose responder defined as a participant in biochemical control at the 08:00 hours assessment after 52 weeks of randomized treatment (where in biochemical control is defined as an A4 concentration equal to or below the upper limit for optimal control.
- To compare Chronocort to IRHC in terms of total daily dose after 52 weeks of randomized treatment. [52 weeks]
The total daily dose (mg) after 52 weeks of randomized treatment. The difference (Chronocort minus IRHC) between the mean total daily dose after 52 weeks of randomized treatment in each treatment arm will be estimated in the Fatigue Assessment Scale (FAS). Superiority of Chronocort to IRHC with respect to total daily dose after 52 weeks of randomized treatment will be declared if the 95% CI for the difference in means lies wholly below zero, provided that dose superiority of Chronocort to IRHC has been declared under the first key secondary efficacy objective.
- To compare Chronocort to IRHC in terms of biochemical responders at 4, 10, 16, and 34 weeks after randomization. [4, 10, 16 and 34 weeks after randomization]
Whether or not the participant is a biochemical responder at 08:00 hours at 4, 10, 16 and 34 weeks after randomization are compared between treatment arms by calculating the difference in proportion of participants responding. These outcome variables are to be analyzed in the same manner as the primary efficacy outcome variable.
- To compare Chronocort to IRHC in terms of dose responders at 10, 16, and 34 weeks after randomization. [10, 16 and 34 weeks after randomization]
Whether or not the participant is a dose responder at 08:00 hours at 10, 16 and 34 weeks after randomization are compared between treatment arms by calculating the difference in proportion of participants responding. These outcome variables are to be analyzed in the same manner as the first key secondary outcome variable.
- To compare Chronocort to IRHC in terms of total daily dose at 10, 16, and 34 weeks after randomization. [10, 16 and 34 weeks after randomization]
Total daily dose at 10, 16 and 34 weeks after randomization are compared between treatment arms by calculating the difference in mean total daily dose. These outcome variables are to be analyzed in the same manner as the second key secondary outcome variable.
- To compare Chronocort to IRHC in terms of biochemical control at 10, 16, and 34 weeks after randomization. [4, 10, 16, 34, and 52 weeks after randomization]
Whether or not the participant is in biochemical control (provided total daily dose is not more than 30 mg) at 08:00 hours at 4, 10, 16, 34 and 52 weeks after randomization are compared between treatment arms by calculating the difference in proportion of participants in control.
- To compare Chronocort to IRHC in terms of the impact on 17 OHP range. [4, 10, 16, 34, and 52 weeks after randomization]
The difference between the 08:00 and 13:00 measurements of 17-OHP levels at 4, 10, 16, 34, and 52 weeks after randomization and their changes from baseline will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on A4 range [4, 10, 16, 34, and 52 weeks after randomization]
The difference between the 08:00 and 13:00 measurements of A4 levels at 4, 10, 16, 34, and 52 weeks after randomization and their changes from baseline will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on mean 17-OHP and A4 [4, 10, 16, 34, and 52 weeks after randomization]
The mean of the 08:00 and 13:00 measurements of 17-OHP levels and A4 levels at 4, 10, 16, 34, and 52 weeks after randomization and their changes from baseline will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on glucocorticoid dose - Total daily dose [4, 10, 16, 34, and 52 weeks after randomization]
The total daily glucocorticoid dose at 4, 10, 16, 34, and 52 weeks after randomization will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on glucocorticoid dose - Biochemical control [52 weeks]
The relationship between daily glucocorticoid dose and biochemical control at 52 weeks after randomization will be explored.
- To compare Chronocort to IRHC in terms of changes in menstrual regularity. [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in menstrual regularity (only in pre menopausal women without hysterectomy and not using hormonal contraception) will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on luteinizing hormone (LH) levels. [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in LH levels (men only) will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on testicular adrenal rest tumors (TART) size. [Baseline to 34 and 52 weeks of randomized treatment]
The change from baseline to 34 and 52 weeks of randomized treatment in size of TART (men only) will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on sperm count. [Baseline to 34 and 52 weeks of randomized treatment]
The change from baseline to 34 and 52 weeks of randomized treatment in sperm count (men only) will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on subjective hirsutism in female participants [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in subjective hirsutism using a Visual Analog Scale (VAS) (women only), which is a 10cm scale ranging from 'No Hair' to 'Most Hair Growth Ever Experienced' will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on objective hirsutism in female participants [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in objective hirsutism using the Ferriman-Gallwey score (women only) will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on subjective acne in female participants. [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in subjective acne using a VAS (women only) will be summarized and compared between treatment arms. The scale used is a 10cm scale ranging from 'No Acne' to 'Worst Acne Ever'.
- To compare Chronocort to IRHC in terms of the impact on objective acne in female participants [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in objective acne using the Global Evaluation Acne (GEA) scale (women only) will be summarized and compared between treatment arms. A score of 1 to 5 is given by the Investigator where 0 is 'Clear, no lesions', 1 is 'Almost clear. Almost no lesions', 2 is 'Mild', 3 is 'Moderate', 4 is 'Severe' and 5 is 'Very severe'.
- To compare Chronocort to IRHC in terms of the impact on glycated hemoglobin (HbA1c) levels. [Screening to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from screening to 4, 10, 16, 34, and 52 weeks of randomized treatment in HbA1c levels will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on waist circumference. [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in waist circumference will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on body weight. [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in body weight will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on Quality of Life (QoL) using the self-completed Medical Outcome Study 36-Item Short Form Health Survey (SF-36®) total score and the sub domain of vitality. [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in QoL using the self completed SF-36® total score and the sub domain of vitality will be summarized and compared between treatment arms. The SF-36 measures eight scales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). All components contribute in different proportions to the overall measures. Where the minimum score is 0 and maximum score is 100 and a high score is a more favorable score.
- To compare Chronocort to IRHC in terms of the impact on QoL using the Multidimensional Assessment of Fatigue (MAF). [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The MAF is a 16 item scale that measures fatigue according to four dimensions: degree and severity, distress that it causes, timing of fatigue, and its impact on various activities of daily living, with a range of score from 1 - 10 per item to give a Global Fatigue Score of up to 50 with a high score indicating a worse outcome.
- To compare Chronocort to IRHC in terms of the impact on QoL using the EuroQol 5 level Standardized Health Questionnaire (EQ-5D-5L™). [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in QoL using the EQ-5D-5L™ will be summarized and compared between treatment arms.The EQ-5D-5L is a self-assessed, QoL questionnaire. The scale measures on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Where the minimum score is 0 and maximum score is 100, a high score indicates a more favorable outcome.
- To assess compliance over the study period. [52 weeks]
The percentage treatment compliance between visits and overall will be summarized
Other Outcome Measures
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment [52 weeks]
This is one statistical measure of a combination of outcomes as listed below (menstrual regularity hirsutism, acne, TART, LH levels, sperm count, body weight, HbA1c, waist circumference, SF-36 and MAF). Outcomes for each measure are compared between individuals on a categorical basis - improved/not improved. Summary statistics of the outcomes show which arm has the most overall improvement in health status.
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - Menstrual Regularity [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on menstrual regularity, which is recorded using an electronic participant diary for all pre-menopausal women (only in pre menopausal women without hysterectomy and not using hormonal contraception)
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - Hirsutism [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on hirsutism (female only) using a Visual Analog Scale (VAS), which is a 10cm scale ranging from 'No Hair' to 'Most Hair Growth Ever Experienced' completed by participant and also objective hirsutism will be assessed by Investigator using the Ferriman-Gallway Score. A score of 1 to 4 is given for nine areas of the body. A total score less than 8 is considered normal, a score of 8 to 15 indicates mild hirsutism, and a score greater than 15 indicates moderate or severe hirsutism. A score of 0 indicates absence of terminal hair.
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - Acne [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on subjective acne (female only) using a Visual Analog Scale (VAS), which is a 10cm scale ranging from 'No Acne' to 'Worst Acne Ever' completed by the participant and also objective acne will be assessed using the Global Evaluation Acne (GEA) Scale, where a score of 1 to 5 is given by the Investigator, where 0 is 'Clear, no lesions', 1 is 'Almost clear. Almost no lesions', 2 is 'Mild', 3 is 'Moderate', 4 is 'Severe' and 5 is 'Very severe'.
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - TART size [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on TART size (men only) measured via ultrasound.
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - LH Level [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on LH levels (Men only).
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - Sperm Count [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on the sperm count (men only) measured by testing kit.
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - Body weight [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on body weight measured at every visit, with outer clothing and shoes removed.
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - HbA1c [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on HbA1c measured at each visit after visit 1.
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - Waist Circumference [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on waist circumference measured at every visit.
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - SF-36® [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on the self completed SF-36® total score. The SF-36 measures eight scales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). All components contribute in different proportions to the overall measures. Where the minimum score is 0 and maximum score is 100 and a high score is a more favorable score.
- To compare Chronocort to IRHC in terms of net clinical benefit after 52 weeks of randomized treatment - Multidimensional Assessment of Fatigue (MAF) [52 weeks]
The probability that a randomly chosen participant from the Chronocort arm shows more clinical benefit after 52 weeks of randomized treatment than a randomly chosen participant from the IRHC arm (the probability of net clinical benefit). The comparison between participants will be based on the Multidimensional Assessment of Fatigue (MAF) score. The MAF is a 16 item scale that measures fatigue according to four dimensions: degree and severity, distress that it causes, timing of fatigue, and its impact on various activities of daily living, with a range of score from 1 - 10 per item to give a Global Fatigue Score of up to 50 with a high score indicating a worse outcome.
- To investigate the correlation between biochemical control at 10, 16, 34 and 52 weeks after randomization with the total daily dose at the corresponding timepoints. [10, 16, 34, and 52 weeks of randomized treatment]
At each of 10, 16, 34 and 52 weeks after randomization, investigate the total daily dose of steroid in participants in biochemical control.
- To compare Chronocort to IRHC in terms of the impact on QoL using the remaining self-completed SF-36® sub domains (excluding vitality). [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in QoL using the remaining self-completed SF 36® sub-domains (excluding vitality) will be summarized and compared between treatment arms. The SF-36 measures eight scales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). All components contribute in different proportions to the overall measures. Where the minimum score is 0 and maximum score is 100, a high score is a more favorable score.
- To compare Chronocort to IRHC in terms of the impact on the bone marker of osteocalcin. [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in osteocalcin levels will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on alertness. [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in alertness will be summarized and compared between treatment arms. Alertness will be assessed using a Visual Analog Scale (VAS), which is a 10cm scale ranging from 'Brain Fog: unable to perform normal daily tasks' to 'Fully Alert: able to perform normal daily tasks easily'. A higher score indicates a better outcome.
- To compare Chronocort to IRHC in terms of the impact on 11 ketotestosterone. [52 weeks]
The change from baseline to the end of 52 weeks of randomized treatment in serum 11 ketotestosterone levels will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on dehydroepiandrosterone (DHEA) [52 weeks]
The change from baseline to the end of 52 weeks of randomized treatment in serum DHEA levels will be summarized and compared between treatment arms.
- To compare Chronocort to IRHC in terms of the impact on total testosterone [52 weeks]
The change from baseline to the end of 52 weeks of randomized treatment in serum total testosterone will be summarized and compared between treatment arms by sex.
- To compare Chronocort to IRHC in terms of the impact on follicle stimulating hormone (FSH) levels. [Baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment]
The change from baseline to 4, 10, 16, 34, and 52 weeks of randomized treatment in FSH levels (women only) will be summarized and compared between treatment arms.
- To assess dose changes over the study period - Incidence [52 weeks]
The incidence of dose changes at each visit up to the end of 52 weeks of randomized treatment and overall will be summarized by treatment arm.
- To assess dose changes over the study period - Change in mg [52 weeks]
The extent (in mg) of dose changes at each visit up to the end of 52 weeks of randomized treatment and overall will be summarized by treatment arm.
- To assess preference for treatment. [52 weeks]
Participant preference for assigned treatment after 52 weeks of randomized treatment compared with previous treatments will be summarized by treatment arm. Preference of treatment will be assessed using a Visual Analog Scale (VAS), which is a 10cm scale where 0 indicates 'Strongly agree' and 10 indicates 'Strongly disagree', when asked if the participant prefers the study medication over their usual Hydrocortisone medication.
- To assess the safety and tolerability of Chronocort relative to IRHC. [52 weeks]
The incidence, nature, severity, relatedness, duration, outcome, seriousness and expectedness of treatment emergent adverse events (TEAEs) will be tabulated by treatment arm. AEs of special interest will additionally be tabulated separately, with particular note of adrenal crises.
- To assess the need for use of additional glucocorticoid doses by recording of use of stress dosing rules - Incidence of use [52 weeks]
The use of medication from the stress dosing packs or use of any additional glucocorticoid treatment during the study will be tabulated by treatment arm and recorded as incidence of use.
- To assess the need for use of additional glucocorticoid doses by recording of use of stress dosing rules - Duration of use [52 weeks]
The use of medication from the stress dosing packs or use of any additional glucocorticoid treatment during the study will be tabulated by treatment arm and recorded as duration of use.
- To assess the need for use of additional glucocorticoid doses by recording of use of stress dosing rules - Dose of steroid [52 weeks]
The use of medication from the stress dosing packs or use of any additional glucocorticoid treatment during the study will be tabulated by treatment arm and recorded as dose of steroid (in mg).
- To evaluate the safety of Chronocort compared to IRHC by assessment of safety laboratory assessments by number of participants with changes in safety laboratory assessments. [52 weeks (Assessed at baseline, 4, 10, 16, 34 and 52 weeks)]
Safety laboratory assessments including hematology, clinical chemistry and urinalysis will be conducted at each visit after randomized treatment and their changes from baseline will be summarized by treatment arm and aggregated to number of participants with changes in safety laboratory assessments.
- To evaluate the safety of Chronocort compared to IRHC by assessment of physical examination by number of participants with changes in physical examination. [52 weeks (Assessed at baseline and 52 weeks)]
A full physical examination to assess the participant's general appearance and overall health will be carried out and aggregated to number of participants with changes in physical examination.
- To evaluate the safety of Chronocort compared to IRHC by assessment of vital signs by number of patients with changes in vital signs. [52 weeks (Assessed at baseline, 4, 10, 16, 34 and 52 weeks)]
Vital signs will be measured at baseline, 4, 10, 16, 34 and 52 weeks and their changes from baseline will be summarized by treatment arm and aggregated to number of participants with changes in vital signs.
- To evaluate the safety of Chronocort compared to IRHC by assessment of electrocardiogram (ECG) by number of patients with changes in ECG. [52 weeks (Assessed at baseline and 52 weeks)]
A single 12-lead ECG will be recorded at baseline and 52 weeks and their changes from baseline will be summarized by treatment arm and aggregated to number of participants with changes in ECG.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female participants must be aged 16 years or older at the time of signing the informed consent/assent.
-
In participants aged <18 years, height velocity must be less than 2 cm/year in the last year and puberty must be completed (Tanner stage V).
-
Participants with known classic CAH due to 21 hydroxylase deficiency diagnosed in childhood with documented (at any time) elevated 17-OHP and with or without elevated A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids) and on stable glucocorticoid therapy for a minimum of 3 months.
-
Participants who are receiving fludrocortisone must be on a documented stable dose for a minimum of 3 months prior to enrollment and must have stable renin levels at screening.
-
Female participants of childbearing potential and all male participants must agree to the use of an accepted method of contraception during the study.
-
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and she is either not a woman of childbearing potential (WOCBP) or has a negative pregnancy test at entry into the study. Note: females presenting with oligomenorrhea or amenorrhea who are aged ≤55 years should be considered potentially fertile and therefore should undergo pregnancy testing like all other female participants.
-
Capable of giving signed informed consent/assent which includes compliance with requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria:
-
Clinical or biochemical evidence of hepatic or renal disease e.g. creatinine >2 times the upper limit of normal (ULN) or elevated liver function tests (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] >2 times the ULN).
-
History of bilateral adrenalectomy.
-
History of malignancy (other than basal cell carcinoma successfully treated >26 weeks prior to entry into the study).
-
Participants who have type 1 diabetes or receive regular insulin, have uncontrolled diabetes, or have a screening HbA1c greater than 8%..
-
Persistent signs of adrenal insufficiency or the participant does not tolerate treatment at the end of the 4-week run-in period.
-
Participants with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study.
-
Participants on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH.
-
Co-morbid condition requiring daily administration of a medication or consumption of any material that interferes with the metabolism of glucocorticoids.
-
Participants who are receiving <10 mg hydrocortisone dose at screening or the hydrocortisone dose equivalent.
-
Participants anticipating regular prophylactic use of additional steroids e.g. for strenuous exercise.
-
Participation in another clinical study of an investigational or licensed drug or device within the 12 weeks prior to screening.
-
Inclusion in any natural history or translational research study that would require evaluation of androgen levels during the study period outside of this protocol's assessments.
-
Participants who have previously been exposed to Chronocort in any Diurnal study.
-
Participants who routinely work night shifts and so do not sleep during the usual night-time hours.
-
Participants, who in the opinion of the Investigator, will be unable to comply with the requirements of the protocol.
-
Participants with a known hypersensitivity to any of the components of the Chronocort capsules, the Cortef tablets, or the placebo capsules.
-
Participants with congenital galactosemia, malabsorption of glucose and galactose, or who are lactase deficient.
-
Participants with a body weight of 45 kg or less.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Diurnal Investigational Site in Orange | Orange | California | United States | 92868 |
| 2 | Diurnal Investigational Site in Iowa | Iowa City | Iowa | United States | 52224 |
| 3 | Diurnal Investigational Site in Maryland | Bethesda | Maryland | United States | 20892-1932 |
| 4 | Diurnal Investigational Site in Michigan | Ann Arbor | Michigan | United States | 48109 |
| 5 | Diurnal Investigational Site in Nevada | Las Vegas | Nevada | United States | 89148 |
| 6 | Diurnal Investigational Site in Yokohama-shi | Yokohama-shi | Kanagawa | Japan | |
| 7 | Diurnal Investigational Site in Izumi-shi | Izumi-shi | Osaka | Japan | |
| 8 | Diurnal Investigational Site in Fuchu-Shi | Fuchu-Shi | Tokyo | Japan | 183-8524 |
| 9 | Diurnal Investigational Site in Setagaya-Ku | Setagaya-Ku | Tokyo | Japan | |
| 10 | Diurnal Investigational Site in Shinjuku-ku | Shinjuku-Ku | Tokyo | Japan | 162-8655 |
Sponsors and Collaborators
- Diurnal Limited
Investigators
- Principal Investigator: D Merke, National Institutes of Health Clinical Center, Bethesda, Maryland, US
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DIUR-014