A Phase III Extension Study of Efficacy, Safety and Tolerability of Chronocort® in the Treatment of Congenital Adrenal Hyperplasia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 1
- 主要终点
- Safety and Tolerability - Number of Participants With Adrenal Insufficiency
研究概览
简要总结
Subjects completing study DIUR-005 and those who have already completed study DIUR-003 will be offered the opportunity either to continue Chronocort® therapy or to switch from their current glucocorticoid therapy to Chronocort® in this open-label study.
详细描述
All subjects will have a screening visit prior to the baseline assessment to allow DIUR-006 procedures to be fully explained and informed consent to be given by the subject. For subjects from DIUR-003 this screening visit will include safety blood tests. Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be not be entered into the study.
All subjects will then return for the baseline visit. For subjects entering from study DIUR-003 the full set of baseline assessments will be completed, including 2 blood samples (one at 09:00 and one at 13:00 hours) for 17-OHP and A4. For subjects entering from DIUR-005, test results from their last visit in the feeder study (Visit 4) will be used for this baseline assessment, with the 09:00 and 13:00 hour results taken from the 24-hour hormone profiles conducted at the visit. Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be withdrawn from this study.
Once the baseline assessments are completed, the subjects will be given sufficient Chronocort® to use until the next visit at Week 4. Subjects from study DIUR-005 who were previously on Chronocort® will continue on the same dose of Chronocort® that they were receiving at the end of the feeder study. Subjects from study DIUR-005 on standard therapy and subjects from study DIUR-003 will have their initial dose of Chronocort® determined using the hydrocortisone equivalent of baseline therapy.
All subjects will return to the study centre at 4, 12 and 24 weeks after starting study DIUR-006 for additional blood tests and dose titration, if necessary. Visits thereafter will take place at 6-monthly intervals. If there is a change of dose, an interim visit or phone call will be needed inbetween the 6-monthly visits.
All subjects will receive telephone calls at 3 monthly intervals, and unscheduled visits will be arranged if necessary. Subjects will also be provided with Chronocort® supplies from the study pharmacy at 3-monthly or 6-monthly intervals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with CAH who have successfully completed a clinical trial with the current formulation of Chronocort®.
- •Provision of signed written informed consent.
排除标准
- •Co-morbid condition requiring daily administration of a medication (or use of any medications/supplements) that interferes with the metabolism of glucocorticoids.
- •Clinical or biochemical evidence of hepatic or renal disease. Creatinine over twice the ULN or elevated liver function tests (ALT or AST >2 times ULN]).
- •Females who are pregnant or lactating.
- •Subjects on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH.
- •History of malignancy (other than basal cell carcinoma successfully treated >6 months prior to entry into the study).
- •Subjects with a history of bilateral adrenalectomy.
- •Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study, except for another clinical trial with the current formulation of Chronocort®.
- •Subjects unable to comply with the requirements of the protocol.
- •Subjects who routinely work night shifts and so do not sleep during the usual nighttime hours.
研究组 & 干预措施
Chronocort®
Chronocort® modified release hydrocortisone
干预措施: Hydrocortisone (Drug)
结局指标
主要结局
Safety and Tolerability - Number of Participants With Adrenal Insufficiency
时间窗: Up to approximately 5 years and 11 months
Safety and tolerability of Chronocort® over time, as assessed by signs and symptoms of adrenal insufficiency or over-treatment throughout the study. Signs and symptoms of adrenal insufficiency included sudden weight loss, sudden weight gain, lack of appetite, increased appetite, nausea, vomiting, headache, blurred vision, fatigue, weakness, dizziness, light-headedness, syncope, sleeping difficulties and increased acne. Number of participants who experienced adrenal insufficiency due to glucocorticoid (GC) over replacement and under replacement are reported.
Safety and Tolerability - Number of Participants Who Used Sick Day Medication
时间窗: Up to approximately 5 years and 11 months
Safety and tolerability of Chronocort, as assessed by number of participants who used sick day medication throughout the study. Data are presented for number of participants taking medication from sick day packs and number of participants taking medication that was not from sick day packs.
Safety and Tolerability - Number of Participants Who Experienced at Least One Adrenal Crisis
时间窗: Up to approximately 5 years and 11 months
Safety and tolerability of Chronocort, as assessed by the number of participants who experienced adrenal crises throughout the study. Adrenal crisis was defined as follows: a) Major impairment of general health with at least two of the following signs/symptoms: Hypotension (systolic blood pressure \<100 mmHg); Nausea or vomiting; Severe fatigue; Fever; Somnolence; Hyponatraemia (\<132 mmol/L) or hyperkalaemia (as judged by characteristic electrocardiogram \[ECG\] changes); Hypoglycaemia and b) Parenteral glucocorticoid (hydrocortisone) administration followed by clinical improvement: Grade 1: outpatient care only; Grade 2: hospital care (general ward); Grade 3: admission to intensive care unit; Grade 4: death from adrenal crisis (with or without parenteral glucocorticoid administration).
Safety and Tolerability - Number of Participants With Adverse Events (AEs)
时间窗: Up to approximately 5 years and 11 months
Safety and tolerability of Chronocort, as assessed by the number of participants with at least 1 AE per specified AE category throughout the study. An AE was any untoward medical occurrence in a participant administered the study drug that did not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, was a congenital anomaly or birth defect, was infection that required treatment parenteral antibiotics, other important medical events which based on medical or scientific judgement might jeopardize the participants, or might require medical or surgical intervention to prevent any of the above. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values
时间窗: Baseline up to approximately 5 years and 11 months
Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline in safety laboratory assessments throughout the study. Participants with a parameter value that shifted from baseline (within reference range) to a value above the reference range for a maximum value on-treatment.
Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values
时间窗: Baseline up to approximately 5 years and 11 months
Safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline in safety laboratory assessments throughout the study. Participants with a parameter value that shifted from baseline (within reference range) to a value below the reference range for a minimum value on-treatment.
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Diastolic Blood Pressure
时间窗: Baseline, Month 30
Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Diastolic blood pressure.
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Systolic Blood Pressure
时间窗: Baseline, Month 30
Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Systolic blood pressure.
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Pulse Rate
时间窗: Baseline, Month 30
Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Pulse rate.
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Respiratory Rate
时间窗: Baseline, Month 30
Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Respiratory rate.
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Temperature
时间窗: Baseline, Month 30
Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - body temperature.
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Weight
时间窗: Baseline, Month 30
Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Body Weight.
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - BMI
时间窗: Baseline, Month 30
Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - BMI.
Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Waist Circumference
时间窗: Baseline, Month 30
Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Waist circumference.
次要结局
- Total Daily Dose of Chronocort in Milligrams (mg)/Day of Hydrocortisone During the Time Interval Baseline to Week 4 and Month 18 to Month 24(Baseline to Week 4 and Month 18-24)
- Total Daily Dose of Chronocort in mg/Day/m^2 of Hydrocortisone by BSA During the Time Interval Baseline to Week 4 and Month 18 to Month 24(Baseline to Week 4 and Month 18-24)
- Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP)(Baseline and Week 24)
- Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4)(Baseline and Week 24)
- Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - C-Terminal Cross-linked Telopeptide (CTX)(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in Fasting Insulin(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in Fasting Glucose(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in Glycated Hemoglobin (HbA1c)(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in High Sensitivity C-reactive Protein (hsCRP)(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in Plasma Renin Activity (PRA)(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Lean Mass(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Bone Mineral Density(Baseline, Month 24)
- Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Fat Mass(Baseline, Month 24)
- Change From Pre-Chronocort Baseline in Quality of Life - Medical Outcome Short Form Health Survey Form 36 (SF-36) Score at Months 12 and 18(Baseline, Months 12 and 18)
- Change From Pre-Chronocort Baseline in Quality of Life - Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI) Score at Months 12 and 18(Baseline, Months 12 and 18)
- Change From Pre-Chronocort Baseline in Quality of Life - Standardized Health Questionnaire 5-Dimension (EQ-5D) Index Score and Visual Analogue Scale (VAS) Score at Months 12 and 18(Baseline, Months 12 and 18)
- Number of Participants With Dose Titrations(Baseline to Week 4 and Month 18)