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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.
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 Any subjects not meeting the inclusion/exclusion criteria following these blood tests will be withdrawn from this study.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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronocort® | Experimental | Chronocort® modified release hydrocortisone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydrocortisone | Drug | Modified release hydrocortisone |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability - Number of Participants With Adrenal Insufficiency | 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. | Up to approximately 5 years and 11 months |
| Safety and Tolerability - Number of Participants Who Used Sick Day Medication | 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. | Up to approximately 5 years and 11 months |
| Safety and Tolerability - Number of Participants Who Experienced at Least One Adrenal Crisis | 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). | Up to approximately 5 years and 11 months |
| Safety and Tolerability - Number of Participants With Adverse Events (AEs) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Total daily dose was summarized in mg/day of hydrocortisone where 1 mg of Chronocort equals 1 mg of hydrocortisone. Baseline was defined as the first visit of Study DIUR-006 for all participants. | Baseline to Week 4 and Month 18-24 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Principal Investigator | Neurocrine UK Limited | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892-1932 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33527139 | Derived | Merke DP, Mallappa A, Arlt W, Brac de la Perriere A, Linden Hirschberg A, Juul A, Newell-Price J, Perry CG, Prete A, Rees DA, Reisch N, Stikkelbroeck N, Touraine P, Maltby K, Treasure FP, Porter J, Ross RJ. Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2063-e2077. doi: 10.1210/clinem/dgab051. |
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This was a Phase 3, open-label extension study. Participants who completed studies DIUR-003 (NCT01735617) or DIUR-005 (NCT02716818) were offered the opportunity to continue Chronocort® therapy in this study. After screening, all participants underwent a full set of baseline assessments before starting treatment in this extension study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Chronocort® | Participants who entered immediately from Study DIUR-005 who were previously on Chronocort (modified release hydrocortisone) continued on the same dose of Chronocort that they had been receiving at the end of the feeder study. All other participants had their initial dose of Chronocort determined using the hydrocortisone equivalent of their current treatment (immediately prior to the baseline visit). Dosing was adjusted on an individual participant basis by investigators using symptoms and signs of disease with 17-hydroxyprogesterone (17-OHP) and androstenedione evaluation to guide dose adjustment. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
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| ID | Title | Description |
|---|---|---|
| BG000 | Chronocort® | Participants who entered immediately from Study DIUR-005 who were previously on Chronocort (modified release hydrocortisone) continued on the same dose of Chronocort that they had been receiving at the end of the feeder study. All other participants had their initial dose of Chronocort determined using the hydrocortisone equivalent of their current treatment (immediately prior to the baseline visit). Dosing was adjusted on an individual participant basis by investigators using symptoms and signs of disease with 17-OHP and androstenedione evaluation to guide dose adjustment. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety and Tolerability - Number of Participants With Adrenal Insufficiency | 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. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. | Posted | Count of Participants | Participants | Up to approximately 5 years and 11 months |
|
From first dose of study drug administration up to approximately 5 years and 11 months
The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Chronocort® | Participants who entered immediately from Study DIUR-005 who were previously on Chronocort (modified release hydrocortisone) continued on the same dose of Chronocort that they had been receiving at the end of the feeder study. All other participants had their initial dose of Chronocort determined using the hydrocortisone equivalent of their current treatment (immediately prior to the baseline visit). Dosing was adjusted on an individual participant basis by investigators using symptoms and signs of disease with 17-OHP and androstenedione evaluation to guide dose adjustment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Appendicitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute sinusitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials Information | Diurnal Limited | +44 (0) 292 068 2069 | info@diurnal.co.uk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 16, 2022 | Jul 13, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 12, 2022 | Jul 13, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000312 | Adrenal Hyperplasia, Congenital |
| ID | Term |
|---|---|
| D047808 | Adrenogenital Syndrome |
| D012734 | Disorders of Sex Development |
| D014564 | Urogenital Abnormalities |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D006854 | Hydrocortisone |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
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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. |
| Up to approximately 5 years and 11 months |
| Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | 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. | Baseline up to approximately 5 years and 11 months |
| Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | 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. | Baseline up to approximately 5 years and 11 months |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Diastolic Blood Pressure | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Diastolic blood pressure. | Baseline, Month 30 |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Systolic Blood Pressure | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Systolic blood pressure. | Baseline, Month 30 |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Pulse Rate | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Pulse rate. | Baseline, Month 30 |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Respiratory Rate | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Respiratory rate. | Baseline, Month 30 |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Temperature | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - body temperature. | Baseline, Month 30 |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Weight | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Body Weight. | Baseline, Month 30 |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - BMI | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - BMI. | Baseline, Month 30 |
| Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Waist Circumference | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Waist circumference. | Baseline, Month 30 |
| 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 | Total daily dose of Chronocort per BSA was summarized in mg/day/m^2 of hydrocortisone where 1 mg of Chronocort equals 1 mg of hydrocortisone. The BSA (m^2) was calculated from baseline values using the Dubois formula [weight (kg)^0.425] x [Height (cm)^0.725)] x 0.007184. Baseline was defined as the first visit of Study DIUR-006 for all participants. | 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) | Long-term efficacy of Chronocort, as assessed by participants achieving disease control at 09:00 hours and 13:00 hours for 17-OHP. Data are presented for the number of participants considered responders and non-responders. A participant was considered a responder if their results were in the optimal range (defined as 1.2 to 36.4 nanomoles [nmol]/liter [L]) for 17-OHP. | Baseline and Week 24 |
| Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | Long-term efficacy of Chronocort, as assessed by participants achieving disease control at 09:00 hours and 13:00 hours for A4. Data are presented for the number of participants considered responders and non-responders. A participant was considered a responder if their results were in the reference range (defined as 1.4 to 5.2 nmol/L in males and 1.0 to 7.0 nmol/L in females) for A4. | Baseline and Week 24 |
| Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin | Long-term efficacy of Chronocort, as assessed by 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) | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in bone turnover markers - CTX. | Baseline, Month 24 |
| Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone | Long-term efficacy of Chronocort, as assessed by 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 | Long-term efficacy of Chronocort, as assessed by 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 | Long-term efficacy of Chronocort, as assessed by 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) | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in HbA1c. | Baseline, Month 24 |
| Change From Pre-Chronocort Baseline at Month 24 in High Sensitivity C-reactive Protein (hsCRP) | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in hsCRP. | Baseline, Month 24 |
| Change From Pre-Chronocort Baseline at Month 24 in Plasma Renin Activity (PRA) | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in PRA. | Baseline, Month 24 |
| Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Lean Mass | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (Dual energy X-ray absorptiometry [DEXA]) - total lean mass | Baseline, Month 24 |
| Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Bone Mineral Density | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - bone mineral density. | Baseline, Month 24 |
| Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Fat Mass | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - 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 | The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Scores of the first four health items (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. Scores of last four items (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. | 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 | MAF is a 16-item scale that measures fatigue according to 4 dimensions; degree and severity, distress that it causes, timing of fatigue, and its impact of various activities of daily living. The GFI score was calculated using a standard method specific to the MAF questionnaire. This combines the responses to the questionnaire to give one score ranging from 1 (no fatigue) to 50 (severe fatigue), with a higher score indicating more severe fatigue, fatigue distress, or impact on activities of daily living. Decreases from baseline indicate improvement. | 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 | The EQ-5D questionnaire consists of 2 parts, the EQ-5D descriptive system and the EQ VAS. The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression each with 5 problem levels (1-none to 5-extreme). The results from the dimensions were combined using a standard method specially designed for the EQ-5D questionnaire to give a single index value (EuroQol Research Foundation) with scores ranging from 0 (no problems) to 1 (extreme problems). The EQ VAS is a visual scale in which the participant gives a single score between 0 (worst health state) and 100 (best health state). | Baseline, Months 12 and 18 |
| Number of Participants With Dose Titrations | Long-term efficacy of Chronocort, as assessed by number of participants with dose titrations. Data are presented for number of participants with a dose increase, dose decrease, both a dose increase, and a dose decrease or no dose titration at specified timepoints. | Baseline to Week 4 and Month 18 |
| Physician Decision |
|
| Pregnancy |
|
| Withdrawal by Subject |
|
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | centimeters (cm) |
|
| Body Weight | Mean | Standard Deviation | kilograms (kg) |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/square meter (m^2) |
|
| Body Surface Area (BSA) | Mean | Standard Deviation | m^2 |
|
| Waist Circumference | Mean | Standard Deviation | cm |
|
| Time Since Congenital Adrenal Hyperplasia (CAH) Diagnosis | Mean | Standard Deviation | years |
|
| Number of Participants Hospitalized Within the Last 12 Months Prior to Enrolment | Count of Participants | Participants |
|
| Number of Participants With Adrenal Crises in the Last Year | Count of Participants | Participants |
|
| Diastolic Blood Pressure | Mean | Standard Deviation | millimeters of mercury (mmHg) |
|
| Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Pulse Rate | Mean | Standard Deviation | beats/minute |
|
| Respiratory Rate | Mean | Standard Deviation | breaths/minute |
|
| Body Temperature | Mean | Standard Deviation | degrees Celsius (°C) |
|
Participants who entered immediately from Study DIUR-005 who were previously on Chronocort (modified release hydrocortisone) continued on the same dose of Chronocort that they had been receiving at the end of the feeder study. All other participants had their initial dose of Chronocort determined using the hydrocortisone equivalent of their current treatment (immediately prior to the baseline visit). Dosing was adjusted on an individual participant basis by investigators using symptoms and signs of disease with 17-OHP and androstenedione evaluation to guide dose adjustment.
|
|
| Primary | Safety and Tolerability - Number of Participants Who Used Sick Day Medication | 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. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. | Posted | Count of Participants | Participants | Up to approximately 5 years and 11 months |
|
|
|
| Primary | Safety and Tolerability - Number of Participants Who Experienced at Least One Adrenal Crisis | 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). | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. | Posted | Count of Participants | Participants | Up to approximately 5 years and 11 months |
|
|
|
| Primary | Safety and Tolerability - Number of Participants With Adverse Events (AEs) | 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. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. | Posted | Count of Participants | Participants | Up to approximately 5 years and 11 months |
|
|
|
| Primary | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Maximum Values | 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. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. Number analyzed for each parameter = participants with a normal parameter value (within reference range) at baseline and also with at least one on-treatment value. | Posted | Count of Participants | Participants | Baseline up to approximately 5 years and 11 months |
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|
|
| Primary | Safety Laboratory Assessments - Number of Participants With a Shift in Laboratory Parameters Baseline Values to the Minimum Values | 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. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. Number analyzed for each parameter = participants with a normal parameter value (within reference range) at baseline and also with at least one on-treatment value. | Posted | Count of Participants | Participants | Baseline up to approximately 5 years and 11 months |
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| Primary | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Diastolic Blood Pressure | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Diastolic blood pressure. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | mmHg | Baseline, Month 30 |
|
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| Primary | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Systolic Blood Pressure | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Systolic blood pressure. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | mmHg | Baseline, Month 30 |
|
|
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| Primary | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Pulse Rate | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Pulse rate. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | beats/minute | Baseline, Month 30 |
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| Primary | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Respiratory Rate | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Respiratory rate. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | breaths/minute | Baseline, Month 30 |
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| Primary | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Temperature | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - body temperature. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | °C | Baseline, Month 30 |
|
|
|
| Primary | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Body Weight | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Body Weight. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | kg | Baseline, Month 30 |
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|
| Primary | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - BMI | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - BMI. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | kg/m^2 | Baseline, Month 30 |
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|
| Primary | Safety and Tolerability - Change From Pre-Chronocort Baseline to Month 30 in Vital Signs - Waist Circumference | Long-term safety and tolerability of Chronocort, as assessed by change from pre-Chronocort baseline to Month 30 in vital signs - Waist circumference. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. | Posted | Mean | Standard Deviation | cm | Baseline, Month 30 |
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|
| Secondary | 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 | Total daily dose was summarized in mg/day of hydrocortisone where 1 mg of Chronocort equals 1 mg of hydrocortisone. Baseline was defined as the first visit of Study DIUR-006 for all participants. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Median | Full Range | mg/day | Baseline to Week 4 and Month 18-24 |
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|
| Secondary | 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 | Total daily dose of Chronocort per BSA was summarized in mg/day/m^2 of hydrocortisone where 1 mg of Chronocort equals 1 mg of hydrocortisone. The BSA (m^2) was calculated from baseline values using the Dubois formula [weight (kg)^0.425] x [Height (cm)^0.725)] x 0.007184. Baseline was defined as the first visit of Study DIUR-006 for all participants. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Median | Full Range | mg/day/m^2 | Baseline to Week 4 and Month 18-24 |
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| Secondary | Number of Participants Achieving Disease Control at 09:00 Hours and 13:00 Hours for 17-hydroxyprogesterone (17-OHP) | Long-term efficacy of Chronocort, as assessed by participants achieving disease control at 09:00 hours and 13:00 hours for 17-OHP. Data are presented for the number of participants considered responders and non-responders. A participant was considered a responder if their results were in the optimal range (defined as 1.2 to 36.4 nanomoles [nmol]/liter [L]) for 17-OHP. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoints. | Posted | Count of Participants | Participants | Baseline and Week 24 |
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| Secondary | Number of Participants Achieving Disease Control at 09:00 Hours and 13.00 Hours for Androstenedione (A4) | Long-term efficacy of Chronocort, as assessed by participants achieving disease control at 09:00 hours and 13:00 hours for A4. Data are presented for the number of participants considered responders and non-responders. A participant was considered a responder if their results were in the reference range (defined as 1.4 to 5.2 nmol/L in males and 1.0 to 7.0 nmol/L in females) for A4. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoints. | Posted | Count of Participants | Participants | Baseline and Week 24 |
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| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - Osteocalcin | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in bone turnover markers (osteocalcin). | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | micrograms (µg)/L | Baseline, Month 24 |
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|
| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Bone Turnover Markers - C-Terminal Cross-linked Telopeptide (CTX) | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in bone turnover markers - CTX. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | nanograms (ng)/L | Baseline, Month 24 |
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|
| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Total Testosterone | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in total testosterone. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. Overall number of participants analyzed = number of male or female participants with evaluable data for the outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | nmol/L | Baseline, Month 24 |
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|
|
| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Fasting Insulin | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in fasting insulin. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | picomoles (pmol)/L | Baseline, Month 24 |
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| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Fasting Glucose | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in fasting glucose. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | millimoles (mmol)/L | Baseline, Month 24 |
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| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Glycated Hemoglobin (HbA1c) | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in HbA1c. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | percentage of HbA1c | Baseline, Month 24 |
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| Secondary | Change From Pre-Chronocort Baseline at Month 24 in High Sensitivity C-reactive Protein (hsCRP) | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in hsCRP. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | mg/L | Baseline, Month 24 |
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| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Plasma Renin Activity (PRA) | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in PRA. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | ng/liter (L)/second | Baseline, Month 24 |
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| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Lean Mass | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (Dual energy X-ray absorptiometry [DEXA]) - total lean mass | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | kg | Baseline, Month 24 |
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| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Bone Mineral Density | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - bone mineral density. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | grams (g)/square centimeter (cm^2) | Baseline, Month 24 |
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| Secondary | Change From Pre-Chronocort Baseline at Month 24 in Body Composition - Total Fat Mass | Long-term efficacy of Chronocort, as assessed by change from pre-Chronocort baseline at Month 24 in body composition (DEXA) - total fat mass | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | kg | Baseline, Month 24 |
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| Secondary | 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 | The SF-36 questionnaire has 36 questions composing the scale that represent 8 domains: 1) physical functioning, role physical, 2) bodily pain, 3) general health, 4) vitality, 5) social functioning, 6) role, 7) emotional, and 8) mental health. The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Scores of the first four health items (1 - 4) were aggregated to derive the PCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. Scores of last four items (5 - 8) were aggregated to derive the MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified category. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Months 12 and 18 |
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| Secondary | Change From Pre-Chronocort Baseline in Quality of Life - Multidimensional Assessment of Fatigue (MAF) Global Fatigue Index (GFI) Score at Months 12 and 18 | MAF is a 16-item scale that measures fatigue according to 4 dimensions; degree and severity, distress that it causes, timing of fatigue, and its impact of various activities of daily living. The GFI score was calculated using a standard method specific to the MAF questionnaire. This combines the responses to the questionnaire to give one score ranging from 1 (no fatigue) to 50 (severe fatigue), with a higher score indicating more severe fatigue, fatigue distress, or impact on activities of daily living. Decreases from baseline indicate improvement. | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Months 12 and 18 |
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| Secondary | 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 | The EQ-5D questionnaire consists of 2 parts, the EQ-5D descriptive system and the EQ VAS. The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression each with 5 problem levels (1-none to 5-extreme). The results from the dimensions were combined using a standard method specially designed for the EQ-5D questionnaire to give a single index value (EuroQol Research Foundation) with scores ranging from 0 (no problems) to 1 (extreme problems). The EQ VAS is a visual scale in which the participant gives a single score between 0 (worst health state) and 100 (best health state). | The Full Analysis Set included all participants who entered the extension study and who subsequently received at least 1 dose of Chronocort. 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 'Number analyzed' signifies participants evaluable for specified category. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Months 12 and 18 |
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| Secondary | Number of Participants With Dose Titrations | Long-term efficacy of Chronocort, as assessed by number of participants with dose titrations. Data are presented for number of participants with a dose increase, dose decrease, both a dose increase, and a dose decrease or no dose titration at specified timepoints. | Full Analysis Set. 'Number analyzed' signifies participants evaluable at specified timepoint. | Posted | Count of Participants | Participants | Baseline to Week 4 and Month 18 |
|
|
|
| 1 |
| 91 |
| 28 |
| 91 |
| 90 |
| 91 |
| COVID-19 | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Gastroenteritis norovirus | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Kidney infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
|
| Haemangiopericytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
|
| Malignant haemangiopericytoma metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA 23.0 | Systematic Assessment |
|
| Adrenocortical insufficiency acute | Endocrine disorders | MedDRA 23.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Suicide attempt | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Loss of consciousness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Myocardial infarction | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Brachiocephalic vein thrombosis | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Diverticulum | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 23.0 | Systematic Assessment | At risk population was based on maternal or paternal exposure. |
|
| Neonatal disorder | Pregnancy, puerperium and perinatal conditions | MedDRA 23.0 | Systematic Assessment | At risk population was based on maternal or paternal exposure. |
|
| Vulvovaginal inflammation | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Red blood cell microcytes | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Subcutaneous haematoma | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Knee arthroplasty | Surgical and medical procedures | MedDRA 23.0 | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Bacterial vaginosis | Infections and infestations | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Balanitis candida | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Fungal infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Fungal skin infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Gastroenteritis norovirus | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Gingivitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Helicobacter infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Localised infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Otitis externa | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pharyngitis streptococcal | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Pulpitis dental | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
|
| Vulval abscess | Infections and infestations | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Vulvovaginitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Adrenal rest tumour of the testis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only male participants were at risk. |
|
| Carcinoid tumour of the small bowel | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Allergy to arthropod bite | Immune system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Allergy to chemicals | Immune system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Thyroid mass | Endocrine disorders | MedDRA 23.0 | Systematic Assessment |
|
| Thyroiditis subacute | Endocrine disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abnormal weight gain | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Increased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Iron deficiency | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Adjustment disorder | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Anticipatory anxiety | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Bipolar I disorder | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Libido decreased | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Panic attack | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Stress | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
|
| Ageusia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Anosmia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Carpal tunnel syndrome | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Circadian rhythm sleep disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Clumsiness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Poor quality sleep | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Taste disorder | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Tension headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Episcleritis | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Optic ischaemic neuropathy | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
|
| Excessive cerumen production | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
|
| Tympanic membrane perforation | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Rebound tachycardia | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Peripheral venous disease | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Respiration abnormal | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Anal pruritus | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Colitis ulcerative | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Diverticulum | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hiatus hernia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oral disorder | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Teeth brittle | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Alopecia areata | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dermatosis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Lichen planus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Lichen sclerosus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Skin laxity | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Skin striae | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Axillary mass | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Limb mass | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Myositis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Plantar fasciitis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Trigger finger | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Polyuria | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Renal pain | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
|
| Amenorrhoea | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Azoospermia | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only male participants were at risk. |
|
| Breast pain | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment |
|
| Breast tenderness | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Endometrial hyperplasia | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Gynaecomastia | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only male participants were at risk. |
|
| Menometrorrhagia | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Menopausal symptoms | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Menorrhagia | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Menstruation irregular | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Metrorrhagia | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Ovarian cyst | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment |
|
| Premature menopause | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Testicular mass | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only male participants were at risk. |
|
| Testicular pain | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only male participants were at risk. |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Vulvar melanosis | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| BRCA1 gene mutation | Congenital, familial and genetic disorders | MedDRA 23.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Facial pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Injection site dermatitis | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oedema mucosal | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Performance status decreased | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Swelling | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Swelling face | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Therapeutic response unexpected | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vaccination site pain | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Vaccination site swelling | General disorders | MedDRA 23.0 | Systematic Assessment |
|
| Blood androstenedione increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood sodium decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood testosterone decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Blood testosterone increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Bone density decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Bone density increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Eosinophil count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Haematocrit decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Heart rate decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Low density lipoprotein increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Occult blood | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Red blood cell count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Red blood cell microcytes | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Renin decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Renin increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Bone contusion | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Corneal abrasion | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Eye injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Fibula fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Heat stroke | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Hypobarism | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Ligament rupture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Maternal exposure during pregnancy | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only female participants were at risk. |
|
| Meniscus injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Mouth injury | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Patella fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Paternal exposure before pregnancy | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only male participants were at risk. |
|
| Post-traumatic neck syndrome | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Procedural nausea | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Procedural vomiting | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| Vaccination complication | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
|
| COVID-19 immunisation | Surgical and medical procedures | MedDRA 23.0 | Systematic Assessment |
|
| Gingival graft | Surgical and medical procedures | MedDRA 23.0 | Systematic Assessment |
|
| Tooth extraction | Surgical and medical procedures | MedDRA 23.0 | Systematic Assessment |
|
| Educational problem | Social circumstances | MedDRA 23.0 | Systematic Assessment |
|
| Family stress | Surgical and medical procedures | MedDRA 23.0 | Systematic Assessment |
|
| Impaired work ability | Social circumstances | MedDRA 23.0 | Systematic Assessment |
|
| Physical assault | Social circumstances | MedDRA 23.0 | Systematic Assessment |
|
| Stress at work | Social circumstances | MedDRA 23.0 | Systematic Assessment |
|
| Ear deformity acquired | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
|
| Foreign body sensation in eyes | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 23.0 | Systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
|
| c-reactive protein decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
|
| Alcohol intolerance | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Gluten sensitivity | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Hyperinsulinaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Impaired fasting glucose | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
|
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
| Sensory loss | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 23.0 | Systematic Assessment | This is a sex-specific AE, only male participants were at risk. |
|
| Blister | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
Sponsor & PI will prepare of manuscripts. Comments on publications will be considered by authors. Publications will not include company confidential details without Sponsor permission. Summary data may be announced to comply with Financial & Regulatory Authorities, while ensuring this will not impact the investigator's ability to publish. Announcements made prior to publication will be reviewed & approved by PI. Data from individual sites will only be published under exceptional circumstances.
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D043202 | Steroid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D015062 | 11-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D015065 | 17-Hydroxycorticosteroids |
| Title | Measurements |
|---|---|
|
| Any AE leading to sick day rules causally related to Chronocort |
|
| Any AE leading to adrenal crisis |
|
| Any AE leading to adrenal crisis causally related to Chronocort |
|
| Any AE of unexpected therapeutic benefit |
|
| Any AE of unexpected therapeutic benefit causally related to Chronocort |
|
| Any AE leading to death |
|
| Any AE leading to death causally related to Chronocort |
|
| Any AE leading to discontinuation |
|
| Any AE leading to discontinuation causally related to Chronocort |
|
| Any serious adverse event (SAE) |
|
| Any SAE causally related to Chronocort |
|
| Any SAE leading to discontinuation |
|
| Any severe AE |
|
| Any severe AE causally related to Chronocort |
|
| Any AE associated with a dose increase |
|
| Any AE associated with a dose increase causally related to Chronocort |
|
| Any AE associated with a dose decrease |
|
| Any AE associated with a dose decrease causally related to Chronocort |
|
| Any AE associated with a dose interruption |
|
| Any AE associated with a dose interruption causally related to Chronocort |
|
| Haemoglobin |
|
|
| Haematocrit |
|
|
| Red cell distribution width |
|
|
| Mean corpuscular volume |
|
|
| Mean cell haemoglobin |
|
|
| Mean cell haemoglobin concentration |
|
|
| Platelet count |
|
|
| Total White Blood Cell Count |
|
|
| Lymphocyte count absolute |
|
|
| Lymphocyte count percentage (%) |
|
|
| Monocyte count absolute |
|
|
| Monocyte count % |
|
|
| Neutrophil count absolute |
|
|
| Neutrophil count % |
|
|
| Basophil count absolute |
|
|
| Basophil count % |
|
|
| Eosinophil count absolute |
|
|
| Eosinophil count % |
|
|
| Sodium |
|
|
| Potassium |
|
|
| Chloride |
|
|
| Total carbon dioxide |
|
|
| Total calcium |
|
|
| Total magnesium |
|
|
| Inorganic phosphorus |
|
|
| Creatinine |
|
|
| Blood urea nitrogen |
|
|
| Fasting glucose |
|
|
| Uric acid |
|
|
| Total protein |
|
|
| Albumin |
|
|
| Alkaline phosphatase |
|
|
| Alanine transaminase (ALT) / glutamate-pyruvate transaminase (GPT) |
|
|
| Aspartate aminotransferase (AST) / glutamic oxaloacetic transaminase (GOT) |
|
|
| Total creatine kinase |
|
|
| Lactate dehydrogenase |
|
|
| Total bilirubin |
|
|
| Direct bilirubin |
|
|
| Total cholesterol |
|
|
| High Density Lipoprotein (HDL) cholesterol |
|
|
| Low density lipoprotein (LDL) cholesterol |
|
|
| Triglycerides |
|
|
| Haemoglobin |
|
|
| Haematocrit |
|
|
| Red cell distribution width |
|
|
| Mean corpuscular volume |
|
|
| Mean cell haemoglobin |
|
|
| Mean cell haemoglobin concentration |
|
|
| Platelet count |
|
|
| Total White Blood Cell Count |
|
|
| Lymphocyte count absolute |
|
|
| Lymphocyte count % |
|
|
| Monocyte count absolute |
|
|
| Monocyte count % |
|
|
| Neutrophil count absolute |
|
|
| Neutrophil count % |
|
|
| Basophil count absolute |
|
|
| Basophil count % |
|
|
| Eosinophil count absolute |
|
|
| Eosinophil count % |
|
|
| Sodium |
|
|
| Potassium |
|
|
| Chloride |
|
|
| Total carbon dioxide |
|
|
| Total calcium |
|
|
| Total magnesium |
|
|
| Inorganic phosphorus |
|
|
| Creatinine |
|
|
| Blood urea nitrogen |
|
|
| Fasting glucose |
|
|
| Uric acid |
|
|
| Total protein |
|
|
| Albumin |
|
|
| Alkaline phosphatase |
|
|
| Alanine transaminase (ALT) / glutamate-pyruvate transaminase (GPT) |
|
|
| Aspartate aminotransferase (AST) / glutamic oxaloacetic transaminase (GOT) |
|
|
| Total creatine kinase |
|
|
| Lactate dehydrogenase |
|
|
| Total bilirubin |
|
|
| Direct bilirubin |
|
|
| Total cholesterol |
|
|
| High Density Lipoprotein (HDL) cholesterol |
|
|
| Low density lipoprotein (LDL) cholesterol |
|
|
| Triglycerides |
|
|
|
|
| 09:00 17-OHP : Week 24 |
|
|
| 13:00 17-OHP : Baseline |
|
|
| 13:00 17-OHP : Week 24 |
|
|
| 09:00 A4 : Week 24 |
|
|
| 13:00 A4 : Baseline |
|
|
| 13:00 A4 : Week 24 |
|
|
|
|
| Total Testosterone, Change at Month 24 |
|
|
|
|
|
|
|
|
|
|
|
| PCS, Change at Month 12 |
|
|
| PCS, Change at Month 18 |
|
|
|
|
| EQ VAS Score, Change at Month 12 |
|
|
| EQ VAS Score, Change at Month 18 |
|
|
| Had both a dose increase and a dose decrease |
|
| No dose titration |
|
| Month 18 |
|
|