NCT03532022撤回3 期
An Open-label, Randomized, Titration-blinded, Phase III Study of Efficacy, Safety and Tolerability Of Chronocort® Compared With Standard Glucocorticoid REeplacement Therapy in the Treatment of Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Non-inferiority of Chronocort® versus standard care in terms of responder rate.
研究概览
简要总结
This study is an open-label, randomised, titration-blinded, parallel arm, multicenter study to compare twice daily Chronocort® with standard care in participants with Congenital Adrenal Hyperplasia (CAH). This study will be conducted in the USA.
详细描述
It will compare the efficacy, safety and tolerability of twice daily Chronocort® with standard care (using the participant's usual individualized standard glucocorticoid regimen) over a treatment period of 52 weeks in participants aged 16 years and over with known CAH due to 21-hydroxylase deficiency (classic CAH) diagnosed in childhood with documented (at any time) elevated 17-OHP or A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants are eligible to be included in the study only if all of the following criteria apply (note: if a participant fails to meet an inclusion criterion, re-screening is permitted if the Investigator considers that the circumstances leading to screening failure will not be relevant when the participant is re-screened at a later time):
- •Participant must be aged 16 years or older at the time of signing the informed consent.
- •In participants aged <18 years, height velocity must be less than 2 cm in the last year and puberty must be completed.
- •Type of Participant and Disease Characteristics
- •Participants with known CAH due to 21-hydroxylase deficiency (classic CAH) diagnosed in childhood with documented (at any time) elevated 17-OHP or A4 and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids).
- •Male and female participants
- •Male participants:
- •- A male participant must agree to use contraception as detailed in Section 10.4 of this protocol during the treatment period and refrain from donating sperm during this period.
- •Female participants:
- •A female participant is eligible to participate if she is not pregnant (Section 10.4), not breastfeeding, and at least one of the following conditions applies:
- •i. Not a woman of childbearing potential (WOCBP) as defined in Section 10.
- •OR ii. A WOCBP with a negative pregnancy test at entry into the study who agrees to follow the contraceptive guidance in Section 10.4 during the treatment period.
- •Note: females presenting with oligomenorrhea or amenorrhea who are aged ≤55 years should be considered potentially fertile and therefore, as well as undergoing pregnancy testing like all other female participants, will be expected to be using an acceptable method of contraception which should have been ongoing for ≥90 days prior to the study.
- •Informed Consent
- •Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
排除标准
- •Participants are excluded from the study if any of the following criteria apply (note: if a participant meets an exclusion criterion, re-screening is permitted if the Investigator considers that the circumstances leading to screening failure will not be relevant when the participant is re-screened at a later time):
- •Medical Conditions
- •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 any participant who is receiving insulin.
- •Participants with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study.
- •Prior/Concomitant Therapy
- •Participants on regular daily oral steroids for any indication other than CAH. Note: a participant should not be given any steroids (even on an irregular basis) within 5 days of a study visit. If there is a medical need for steroid treatment within this time frame then the visit should be postponed until a 5-day interval has elapsed.
- •Co-morbid condition requiring daily administration of a medication or consumption of any material that interferes with the metabolism of glucocorticoids (examples provided at http://medicine.iupui.edu/clinpharm/ddis/clinical-table/).
- •Participants who are receiving <10 mg hydrocortisone dose at baseline or the hydrocortisone dose equivalent.
- •Prior/Concurrent Clinical Study Experience
- •Participation in another clinical study of an investigational or licensed drug or device within the 12 weeks prior to screening or during the study.
- •Inclusion in any natural history or translational research study that would require evaluation of androgen levels during the study period outside of this study protocol assessments.
- •Participants who have previously been exposed to Chronocort in studies DIUR-003, DIUR-005 or DIUR-
- •Other Exclusions
- •Participants who routinely work night shifts and so do not sleep during the usual night-time hours.
- •Participants unable to comply with the requirements of the protocol.
研究组 & 干预措施
Chronocort
Experimental
Hydrocortisone modified release capsules - Chronocort®. 66 subjects will be randomised to this group using an interactive web response system (IWRS).
干预措施: Chronocort® (Drug)
Standard Care
Active Comparator
Subjects participating in this arm will continue to receive their normal, standard care (hydrocortisone, dexamethasone, prednisone, prednisolone) once enrolled on the study. 66 subjects will be randomised to this arm using an interactive web response system (IWRS).
干预措施: Standard Care (Drug)
结局指标
主要结局
Non-inferiority of Chronocort® versus standard care in terms of responder rate.
时间窗: 52 weeks
The proportion of participants after 52 weeks of treatment in the Chronocort® and standard care treatment groups achieving biochemical control. Participants with 17 OHP and A4 in the optimal (for 17-OHP) and reference range (for A4) at both timepoints of 09:00 and 13:00 hours will be classified as 'in biochemical control'; if at least one of these measurements is outside of the optimal (for 17-OHP) or reference range (for A4) they will be classified as 'not in biochemical control'.
次要结局
- Impact of both treatments on hirsutism in female participants.(Weeks 26 & 52)
- Impact of both treatments on quality of life (QoL) using SF-36® total score and the sub-domain of vitality.(Weeks 26 & 52)
- Safety of Chronocort® compared to standard care by assessment of vital signs - Heart rate(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of urinalysis - pH(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of routine safety haematology assessments - Red cell distribution width (RDW)(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Impact of both treatments on acne.(Weeks 26 & 52)
- Impact of both treatments on waist circumference (in centimetres).(Weeks 26 & 52)
- Impact of both treatments on body weight (in kilograms).(Weeks 26 & 52)
- Impact of both treatments on Quality of Life using EQ-5D™.(Weeks 26 & 52)
- Safety and tolerability of Chronocort® relative to standard care(52 weeks)
- Safety of Chronocort® compared to standard care by assessment of routine safety haematology assessments - mean cell haemoglobin (MCH)(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of routine safety haematology assessments - haemaglobin(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of routine safety haematology assessments - mean corpuscular volume (MCV)(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of routine safety haematology assessments - mean cell haemoglobin concentration (MCHC)(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Impact of both treatments on markers of fertility.(Weeks 26 & 52)
- Impact of both treatments on glycated hemoglobin (HbA1c) levels.(Weeks 26 & 52)
- The need for additional glucocorticoid doses(52 weeks)
- Impact of both treatments on Quality of Life using Multidimensional Assessment of Fatigue (MAF).(Weeks 26 & 52)
- Safety of Chronocort® compared to standard care by assessment of routine safety haematology assessments - Red blood cell count and platelet count(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of routine safety haematology assessments - haematocrit(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of vital signs - Blood pressure(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of urinalysis - Glucose(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of urinalysis - Ketones(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of routine safety haematology assessments - White blood cell count with differential (absolute and %): Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of physical examinations.(Baseline (Day 1), Week 26 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of vital signs - Respiratory rate(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of vital signs - Oral body temperature(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of urinalysis - Specific gravity(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of urinalysis - Bilirubin(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of urinalysis - Urobilinogen by dipstick(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of electrocardiogram (ECG).(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of urinalysis - Proteins(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
- Safety of Chronocort® compared to standard care by assessment of urinalysis - Blood(Baseline (Day 1), Week 2, Week 6, Week 12, Week 26, Week 39 & Week 52)
研究者
研究点 (2)
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