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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-022403-22 | EudraCT Number |
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This exploratory study is a proof of concept study to determine whether LCI699 can safely reduce the level of urinary free cortisol in patients with Cushing's disease.
In addition, this study evaluated the long term efficacy and safety of LCI699 including an additional 12 week of treatment followed by a 12 month long term optional extension.
A second extension provided patients who were clinically benefitting from LCI699 an opportunity to continue to have access to the drug until LCI699 was commercially available and reimbursed or through the availability of a local access program.
The Primary objective of this study was to assess the effect of 10-week treatment osilodrostat on 24 hour urine free cortisol (UFC) in patients with Cushing's disease.
The study consisted of a screening period of up to 60 days (to allow an adequate washout period for any medications that modified cortisol levels), a 10-14-day baseline period, a 10-week sequential dose escalation treatment period and a 14-day washout period followed by a Study Completion evaluation approximately 14 days after the last drug administration. Twelve patients were recruited and completed Part l of the study.
Eligible patients were dosed at 2 mg b.i.d for the first two weeks, the dose could then be increased every two weeks as necessary (to doses of 5, 10, 20 and 50 mg b.i.d). If at anytime, the subject's UFC was < Upper Limit of Normal (ULN), dose escalation was halted and the subject remained on the current, efficacious dose through Week 10, with continued monitoring of UFC responses every 2 weeks to allow continued dose adjustments if necessary. If at any time the subject experienced side effects which were either intolerable or met dose adjustment criteria, the prescribed dose was adjusted.
The primary endpoint (UFC ≤ ULN or ≥50% decrease at Day 70) was achieved by all patients. Subsequently, in order to confirm these observations, protocol was amended (Protocol amendment 4) and new patients were enrolled and investigated for a longer treatment period.
Following Protocol amendment 4, the study design was modified to include patients in Part II of the study for evaluating the long-term efficacy and safety of osilodrostat treatment for 22 weeks. Nineteen patients (15 who were treated in the expansion cohort in Part ll and 4 who participated in Part l) with Cushing's disease were enrolled as part of the Expansion cohort in Part II of the study. The 12 patients who had entered the study in Part I, were allowed to re-enter the study as the Core proof of concept (PoC) Follow-up cohort. At Day 70 ± 2 days (Week 10), all patients (both patients entering for the first time and those reentering the study) entered the 12-week assessment period. At Day 154, patients completed the End of Treatment-Core visit.
On Day 154 (Week 22), patients had the option to enter the 12-month extension phase (long-term extension 1). On Day 490, patients who continued in the study had the option to enter a second long term extension phase (extension-2) at the Investigator's discretion, provided they did not meet any of the study discontinuation criteria.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part l: Core cohort | Experimental | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part I of this study. 4 patients in this cohort moved to Part II of the study |
|
| Part II Core: Expansion cohort | Experimental | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part II Core Expansion of this study. These patients were all newly enrolled into the phase II part of the study |
|
| Part II Core: Follow-up cohort | Experimental | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part II Core Follow-up of this study. These patients were patients who transferred from Part I Core phase of the study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LCI699 | Drug | Osilodrostat 1 mg and 5 mg capsules, was prepared by Novartis and supplied to the Investigator. The capsule formulation of osilodrostat was later changed to tablets and this change was implemented in the study with Protocol amendment 6. Osilodrostat was open labeled 1 mg, 5 mg, 10 mg and 20 mg tablets. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Responders to LCI699 Based on the Change in Mean Urinary Free Cortisol (UFC) From Baseline to Week 10 | A patient was considered to be a responder if his/her mean UFC level from the three 24-hour urine samples collected at Week 10 was ≤ Upper Limit of Normal (ULN), as defined by the local laboratories, or represented a ≥50% decrease from baseline. Patients who discontinued for a disease or treatment related reason (e.g. death, adverse event, clinical disease progression etc.), or whose mean Week 10 24-hour UFC levels were higher than the normal limit and experienced <50% decrease in UFC were classified as non-responders. | 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Actual Change From Baseline (BL) in Steroid Hormones of Hypothalamic-Pituitary-Adrenal (HPA)-Axis: 11- Deoxycorticosterone (Overall) | Change in Deoxycorticosterone over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: 11-Deoxycortisol (Overall) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University Endo, Metabolism and Molecular | Chicago | Illinois | 60611-3308 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41052284 | Derived | Fleseriu M, Pivonello R, Lacroix A, Biller BMK, Feelders R, Gadelha M, Bertherat J, Belaya Z, Piacentini A, Pedroncelli AM, Newell-Price J. Osilodrostat dose impact on efficacy/safety in Cushing's disease: large, pooled analysis of LINC 2, 3, and 4. Eur J Endocrinol. 2025 Oct 30;193(5):606-617. doi: 10.1093/ejendo/lvaf207. | |
| 24423285 |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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For overall study: 27 patients were planned; For Part l of the study, 12 - 15 patients were planned to be enrolled. For Part ll Core 19 patients were planned to be enrolled.
31 were enrolled in the study: 12 in Part l and 19 in Part ll Core. Four of the participants in the Part II Core were previously enrolled in the Part I Core.
That is, 4 participants who were included in Part 1 as well as in Part 2, re-enrolled in the study in part 2 (i.e., they completed the informed consent process again in Part 2, and were considered re-enrolled, after originally enrolling in part 1).
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| ID | Title | Description |
|---|---|---|
| FG000 | Part l: Core Cohort | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part l of this study. 4 patients in this cohort moved to Part II of the study |
| FG001 | Part II Core: Expansion Cohort | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. |
| FG002 | Part ll Core: Follow-up Cohort | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part I: Core Study |
| |||||||||||||
| Part II: Core Study |
|
Part l: Core cohort: safety analysis set (SAS): All subjects that received at least one dose of study drug.
Part 2: Expansion cohort: Full Analysis Set (FAS): All patients in Follow-up cohort.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part l: Core Cohort | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part l of this study. 4 patients in this cohort moved to Part II of the study |
| BG001 | Part II Core: Expansion Cohort |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 | Percentage of Responders to LCI699 Based on the Change in Mean Urinary Free Cortisol (UFC) From Baseline to Week 10 | A patient was considered to be a responder if his/her mean UFC level from the three 24-hour urine samples collected at Week 10 was ≤ Upper Limit of Normal (ULN), as defined by the local laboratories, or represented a ≥50% decrease from baseline. Patients who discontinued for a disease or treatment related reason (e.g. death, adverse event, clinical disease progression etc.), or whose mean Week 10 24-hour UFC levels were higher than the normal limit and experienced <50% decrease in UFC were classified as non-responders. | Primary Analysis Set: All patients with evaluable UFC data (at least two 24 hour measurements for both baseline and Week 10) were included in the primary efficacy analysis set. Of the 12 patients enrolled to this arm, 9 of the 12 patients met this criteria. | Posted | Number | Percentage of participants | 10 weeks |
|
Adverse Event (AE) timeframe: Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment, up to maximum duration of 350.6 weeks.
Adverse Event (AE): Any sign or symptom that occurs during the study treatment plus the 28 days post treatment
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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 | Part l: Core Cohort | Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part l of this study. 4 patients in this cohort moved to Part II of the study |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | novartis.email@novartis.com |
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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 | May 3, 2018 | Oct 21, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 13, 2019 | Oct 21, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000308 | Adrenocortical Hyperfunction |
| D047748 | Pituitary ACTH Hypersecretion |
| D010900 | Pituitary Diseases |
| ID | Term |
|---|---|
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
| D006964 | Hyperpituitarism |
| D007027 | Hypothalamic Diseases |
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| ID | Term |
|---|---|
| C553306 | Osilodrostat |
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|
|
Change in Deoxycortisol over time. |
| baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Aldosterone, Thyroxine, Free (T4) | Change in aldosterone & thyroxine, free over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Female) | Change in Estradiol in females over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Male) | Change in Estradiol in males over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (FSH) (Female) | Change in FSH in females over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (Male) | Change in FSH in males over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Renin, Insulin, Thyrotropin | Change in Renin, Insulin & Thyrotropin over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Insulin-like Growth Factor-1 | Change in Insulin-like Growth Factor-1 over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Luteinising Hormone (LH) (Female) | Change in LH in females over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: LH (Male) | Change in LH in males over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Female) | Change in Testosterone in females over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Male) | Change in Testosterone in males over time. | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
| Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Fasting Glucose | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
| Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Hemoglobin A1C (HbA1C) (Glycosylated Hemoglobin) | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
| Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
| Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Sitting Diastolic Blood Pressure (DBP), Sitting Systolic Blood Pressure (SBP) | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
| Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Weight | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
| Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Body Mass Index (BMI) | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
| Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Quantitative Insulin Sensitivity Check Index (QUICKI) | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. QUICKI is the quantitative insulin sensitivity check index and is derived using the inverse of the sum of algorithms (base 10) of the fasting insulin and fasting glucose: 1/(log(fasting insulin mU/mL)+log(fasting glucose mg/dL)). Values typically associated with the QUICKI calculation for insulin resistance in humans fall broadly within a range between 0.45 for unusually healthy individuals and 0.30 in diabetics. So lower numbers reflect greater insulin resistance. | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
| Pharmacokinetics (PK) Parameters: Area Under Curve (AUC)0-6h ss, AUC0-12h ss | Trough PK concentrations and PK profiles at steady-state were collected. The AUC from time 0 to 12 h post dose at steady state, calculated by using the predose concentration (Ctrough,ss) as the 12 h concentration, assuming steady-state has been reached. | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
| PK Parameters: Cmax ss, Ctrough ss | Trough PK concentrations and PK profiles at steady-state were collected. | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
| PK Parameters: Tmax ss, | Trough PK concentrations and PK profiles at steady-state were collected. | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
| PK Parameters: T1/2 ss, | Trough PK concentrations and PK profiles at steady-state were collected. | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
| Percentage of Participants Who Were Responders on 24-hour Urine Free Cortisol (UFC) at Week 22 | A patient was considered to be a responder if his/her mean UFC level from the three 24-hour urine samples collected at Week 22 was ≤ ULN (as defined by the local laboratories) or represented a ≥50% decrease from baseline. Participants with controlled or partially controlled UFC were defined as: Controlled UFC: mean UFC level <= upper limit of normal (ULN). Partially controlled UFC: mean UFC level > ULN but with >= 50% reduction from baseline. | Week 22 |
| Number of Participants With Escape | Escape is defined as loss of UFC control (i.e. UFC > ULN) on at least 2 consecutive visits at the highest tolerated dose after previously attaining UFC normalization) | approx. 7 years |
| Massachusetts General Hospital Neuroendocrine Unit |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Oregon Health and Science University SC | Portland | Oregon | 97239-3098 | United States |
| Novartis Investigative Site | Le Kremlin-Bicêtre | 94275 | France |
| Novartis Investigative Site | Paris | 75014 | France |
| Novartis Investigative Site | Ancona | L60020 | Italy |
| Novartis Investigative Site | Naples | 80131 | Italy |
| Novartis Investigative Site | Sapporo | Hokkaido | 060 8648 | Japan |
| Novartis Investigative Site | Chiba | 260 8677 | Japan |
| Bertagna X, Pivonello R, Fleseriu M, Zhang Y, Robinson P, Taylor A, Watson CE, Maldonado M, Hamrahian AH, Boscaro M, Biller BM. LCI699, a potent 11beta-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing's disease: results from a multicenter, proof-of-concept study. J Clin Endocrinol Metab. 2014 Apr;99(4):1375-83. doi: 10.1210/jc.2013-2117. Epub 2013 Dec 11. |
| NOT COMPLETED |
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|
Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
|
Participants took an ascending dose of LCI699 (osilodrostat) from 2mg bid or 5 mg bid, up to 30 mg bid and participated in Part l of this study. 4 patients in this cohort moved to Part II of the study |
|
|
| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of Hypothalamic-Pituitary-Adrenal (HPA)-Axis: 11- Deoxycorticosterone (Overall) | Change in Deoxycorticosterone over time. | Safety Analysis Set (SAS): All patients in the Core proof of concept (PoC) follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | pmol/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: 11-Deoxycortisol (Overall) | Change in Deoxycortisol over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | nmol/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Aldosterone, Thyroxine, Free (T4) | Change in aldosterone & thyroxine, free over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | pmol/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Female) | Change in Estradiol in females over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the female patients only. | Posted | Mean | Standard Deviation | pmol/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Male) | Change in Estradiol in males over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. | Posted | Mean | Standard Deviation | pmol/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (FSH) (Female) | Change in FSH in females over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the female patients only. | Posted | Mean | Standard Deviation | U/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (Male) | Change in FSH in males over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. | Posted | Mean | Standard Deviation | U/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Renin, Insulin, Thyrotropin | Change in Renin, Insulin & Thyrotropin over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | mU/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Insulin-like Growth Factor-1 | Change in Insulin-like Growth Factor-1 over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | ug/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Luteinising Hormone (LH) (Female) | Change in LH in females over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the female patients only. | Posted | Mean | Standard Deviation | U/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: LH (Male) | Change in LH in males over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. | Posted | Mean | Standard Deviation | U/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Female) | Change in Testosterone in females over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the female patients only. | Posted | Mean | Standard Deviation | nmol/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Male) | Change in Testosterone in males over time. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. | Posted | Mean | Standard Deviation | nmol/L | baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88 |
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| Secondary | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Fasting Glucose | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
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| Secondary | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Hemoglobin A1C (HbA1C) (Glycosylated Hemoglobin) | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | Percentage | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
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| Secondary | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | mmo1/L | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
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|
|
| Secondary | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Sitting Diastolic Blood Pressure (DBP), Sitting Systolic Blood Pressure (SBP) | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | mmHG | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
|
|
|
| Secondary | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Weight | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | Kg | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
|
|
|
| Secondary | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Body Mass Index (BMI) | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | Kg/m^2 | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
|
|
|
| Secondary | Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Quantitative Insulin Sensitivity Check Index (QUICKI) | Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline. QUICKI is the quantitative insulin sensitivity check index and is derived using the inverse of the sum of algorithms (base 10) of the fasting insulin and fasting glucose: 1/(log(fasting insulin mU/mL)+log(fasting glucose mg/dL)). Values typically associated with the QUICKI calculation for insulin resistance in humans fall broadly within a range between 0.45 for unusually healthy individuals and 0.30 in diabetics. So lower numbers reflect greater insulin resistance. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Mean | Standard Deviation | unitless | Baseline, Week 22, Week 70, Last observed value, up to Month 88 |
|
|
|
| Secondary | Pharmacokinetics (PK) Parameters: Area Under Curve (AUC)0-6h ss, AUC0-12h ss | Trough PK concentrations and PK profiles at steady-state were collected. The AUC from time 0 to 12 h post dose at steady state, calculated by using the predose concentration (Ctrough,ss) as the 12 h concentration, assuming steady-state has been reached. | Pharmacokinetic Analysis Set (PAS): all enrolled patients with at least 1 dose of study drug and at least 1 post-dose PK assessment after Protocol Amendment 4 or after re-entering the study. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr•ng/mL | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
|
|
|
| Secondary | PK Parameters: Cmax ss, Ctrough ss | Trough PK concentrations and PK profiles at steady-state were collected. | PAS: all enrolled patients with at least 1 dose of study drug and at least 1 post-dose PK assessment after Protocol Amendment 4 or after re-entering the study. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
|
|
|
| Secondary | PK Parameters: Tmax ss, | Trough PK concentrations and PK profiles at steady-state were collected. | PAS: all enrolled patients with at least 1 dose of study drug and at least 1 post-dose PK assessment after Protocol Amendment 4 or after re-entering the study. | Posted | Median | Full Range | hour (hr) | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
|
|
|
| Secondary | PK Parameters: T1/2 ss, | Trough PK concentrations and PK profiles at steady-state were collected. | PAS: all enrolled patients with at least 1 dose of study drug and at least 1 post-dose PK assessment after Protocol Amendment 4 or after re-entering the study. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour (hr) | pre-dose (0 hour), 1, 1.5, 2, 4 and 6 hours post AM dose for escalation dose or pre-dose (trough) for maintained dose |
|
|
|
| Secondary | Percentage of Participants Who Were Responders on 24-hour Urine Free Cortisol (UFC) at Week 22 | A patient was considered to be a responder if his/her mean UFC level from the three 24-hour urine samples collected at Week 22 was ≤ ULN (as defined by the local laboratories) or represented a ≥50% decrease from baseline. Participants with controlled or partially controlled UFC were defined as: Controlled UFC: mean UFC level <= upper limit of normal (ULN). Partially controlled UFC: mean UFC level > ULN but with >= 50% reduction from baseline. | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. This analysis was on the male patients only. | Posted | Number | 95% Confidence Interval | Percentage pf participants | Week 22 |
|
|
|
| Secondary | Number of Participants With Escape | Escape is defined as loss of UFC control (i.e. UFC > ULN) on at least 2 consecutive visits at the highest tolerated dose after previously attaining UFC normalization) | Safety Analysis Set (SAS): All patients in the Core PoC follow-up cohort who received at least one dose of study treatment after reentering the study and all patients in the Expansion cohort who received at least one dose of study treatment after Protocol amendment 04. | Posted | Number | Participants | approx. 7 years |
|
|
|
| 0 |
| 12 |
| 1 |
| 12 |
| 12 |
| 12 |
| EG001 | Part ll Core: Expansion Cohort | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Expansion of this study. These patients were all newly enrolled into the phase ll part of the study | 0 | 15 | 5 | 15 | 15 | 15 |
| EG002 | Part ll Core: Follow-up Cohort | Participants took an ascending dose from 2mg bid or 5 mg bid, up to 30 mg bid and participated in the Part ll Core Follow-up of this study. These patients were patients who transferred from Part l Core phase of the study | 0 | 4 | 1 | 4 | 4 | 4 |
| Supraventricular extrasystoles | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pituitary-dependent Cushing's syndrome | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.1) | Systematic Assessment |
|
| Pituitary tumour benign | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Takayasu's arteritis | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Polycythaemia | Blood and lymphatic system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Bundle branch block right | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (22.1) | Systematic Assessment |
|
| Inner ear disorder | Ear and labyrinth disorders | MedDRA (22.1) | Systematic Assessment |
|
| Middle ear effusion | Ear and labyrinth disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (22.1) | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
|
| Diabetes insipidus | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
|
| Glucocorticoid deficiency | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pituitary-dependent Cushing's syndrome | Endocrine disorders | MedDRA (22.1) | Systematic Assessment |
|
| Blepharospasm | Eye disorders | MedDRA (22.1) | Systematic Assessment |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA (22.1) | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Gastric disorder | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Irritable bowel syndrome | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Tongue disorder | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Feeling drunk | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (22.1) | Systematic Assessment |
|
| Cholelithiasis | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA (22.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Escherichia urinary tract infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Fungal infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Furuncle | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Gastroenteritis bacterial | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Groin abscess | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Helicobacter gastritis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Onychomycosis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Pharyngitis streptococcal | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Tongue fungal infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Viral rhinitis | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA (22.1) | Systematic Assessment |
|
| Accident | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Animal bite | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Heat illness | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Muscle injury | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (22.1) | Systematic Assessment |
|
| Aldosterone urine increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood aldosterone decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood corticotrophin increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood gonadotrophin abnormal | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood luteinising hormone decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood phosphorus | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood pressure decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood prolactin increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood testosterone free increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood testosterone increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Cortisol decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Cortisol free urine decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Cortisol free urine increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Electrocardiogram T wave abnormal | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Gastric pH decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| High density lipoprotein decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Hormone level abnormal | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Neutrophil count increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Oestradiol increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Protein total increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Renin decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Urine analysis abnormal | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Urine leukocyte esterase | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Vitamin D decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA (22.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Folate deficiency | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypercreatininaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypoproteinaemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hyposideraemia | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA (22.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.1) | Systematic Assessment |
|
| Pituitary tumour benign | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (22.1) | Systematic Assessment |
|
| Cold-stimulus headache | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypersomnia | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypogeusia | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (22.1) | Systematic Assessment |
|
| Abnormal sleep-related event | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
|
| Disorientation | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
|
| Libido decreased | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA (22.1) | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA (22.1) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (22.1) | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA (22.1) | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA (22.1) | Systematic Assessment |
|
| Amenorrhoea | Reproductive system and breast disorders | MedDRA (22.1) | Systematic Assessment |
|
| Breast pain | Reproductive system and breast disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (22.1) | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA (22.1) | Systematic Assessment |
|
| Menorrhagia | Reproductive system and breast disorders | MedDRA (22.1) | Systematic Assessment |
|
| Menstruation delayed | Reproductive system and breast disorders | MedDRA (22.1) | Systematic Assessment |
|
| Oligomenorrhoea | Reproductive system and breast disorders | MedDRA (22.1) | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (22.1) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Laryngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (22.1) | Systematic Assessment |
|
| Acanthosis nigricans | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hair growth abnormal | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hirsutism | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypertrichosis | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Melanoderma | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Papule | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (22.1) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| WK 22: 11-Deoxycorticosterone |
|
|
| WK 70: 11-Deoxycorticosterone |
|
|
| LOV: 11-Deoxycorticosterone |
|
|
| WK 22: 11-Deoxycortisol |
|
|
| WK 70: 11-Deoxycortisol |
|
|
| LOV: 11-Deoxycortisol |
|
|
| WK 22: Aldosterone |
|
|
| WK 70: Aldosterone |
|
|
| LOV: Aldosterone |
|
|
| BL: Thyroxine, free |
|
|
| WK 22: Thyroxine, free |
|
|
| WK 70: Thyroxine, free |
|
|
| LOV: Thyroxine, free |
|
|
| WK 22: Female Estradiol |
|
|
| WK 70: Female Estradiol |
|
|
| LOV: Female Estradiol |
|
|
| WK 22: Male Estradiol |
|
|
| WK 70: Male Estradiol |
|
|
| LOV: Male Estradiol |
|
|
| WK 22: Female FSH |
|
|
| WK 70: Female FSH |
|
|
| LOV: Female FSH |
|
|
| WK 22: Male FSH |
|
|
| WK 70: Male FSH |
|
|
| LOV: Male FSH |
|
|
| WK 22: Renin |
|
|
| WK 70: Renin |
|
|
| LOV: Renin |
|
|
| BL: Insulin |
|
|
| WK 22: Insulin |
|
|
| WK 70: Insulin |
|
|
| LOV: Insulin |
|
|
| BL: Thyrotropin |
|
|
| WK 22: Thyrotropin |
|
|
| WK 70: Thyrotropin |
|
|
| LOV: Thyrotropin |
|
|
| WK 22: Insulin-like Growth Factor-1 |
|
|
| WK 70: Insulin-like Growth Factor-1 |
|
|
| LOV: Insulin-like Growth Factor-1 |
|
|
| WK 22: Female LH |
|
|
| WK 70: Female LH |
|
|
| LOV: Female LH |
|
|
| WK 22: Male LH |
|
|
| WK 70: Male LH |
|
|
| LOV: Male LH |
|
|
| WK 22: Female Testosterone |
|
|
| WK 70: Female Testosterone |
|
|
| LOV: Female Testosterone |
|
|
| WK 22: Male Testosterone |
|
|
| WK 70: Male Testosterone |
|
|
| LOV: Male Testosterone |
|
|
| WK 22 |
|
|
| WK 70 |
|
|
| LOV |
|
|
| WK 22 |
|
|
| WK 70 |
|
|
| LOV |
|
|
| WK 22 Cholesterol |
|
|
| WK 70 Cholesterol |
|
|
| LOV Cholesterol |
|
|
| BL LDL Cholesterol |
|
|
| WK 22 LDL Cholesterol |
|
|
| WK 70 LDL Cholesterol |
|
|
| LOV LDL Cholesterol |
|
|
| BL HDL Cholesterol |
|
|
| WK 22 HDL Cholesterol |
|
|
| WK 70 HDL Cholesterol |
|
|
| LOV HDL Cholesterol |
|
|
| BL Triglycerides |
|
|
| WK 22 Triglycerides |
|
|
| WK 70 Triglycerides |
|
|
| LOV Triglycerides |
|
|
| WK 22 DPB |
|
|
| WK 70 DPB |
|
|
| LOV DPB |
|
|
| BL SBP |
|
|
| WK 22 SPB |
|
|
| WK 70 SPB |
|
|
| LOV SPB |
|
|
| WK 22 |
|
|
| WK 70 |
|
|
| LOV |
|
|
| WK 22 |
|
|
| WK 70 |
|
|
| LOV |
|
|
| WK 22 |
|
|
| WK 70 |
|
|
| LOV |
|
|
|
| AUC0-12h,ss |
|
|
|
| Ctrough, ss |
|
|
| Partially controlled UFC responders |
|