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Study of Efficacy and Safety of Osilodrostat in Cushing's Syndrome

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02468193
Collaborator
(none)
9
Enrollment
4
Locations
1
Arm
37.2
Actual Duration (Months)
2.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study aim was to investigate the efficacy and safety of Osilodrostat in patients with Cushing's syndrome due to causes other than Cushing's disease in Japan.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This was a Phase II, single arm, open-label, dose titration, multi-center study which consisted of two distinct Study Periods plus an optional extension period in non-CD patients with CS. The 3 Study Periods (two distinct Study Periods plus an optional extension period) were as follows:

Study Period I [Week 0 (Day 1) to Week-12]: Study Period I was the dose titration period to achieve a stable therapeutic dose and to assess the efficacy and safety of osilodrostat.

The dosing regimen of osilodrostat in this study was titrated according to the following escalation sequence: osilodrostat 2 mg bid, 5 mg bid, 10 mg bid, 20 mg bid, and 30 mg bid. Dose adjustments were based on the serum cortisol values measured by the local lab at each site. Osilodrostat titration was done weekly for the initial 4-weeks, up to a maximum dose of 10 mg bid.

The mean of three 24-hour UFC (mUFC) values were measured to evaluate the efficacy in this period.

Study Period II (After Week-12 to Week-48): Study Period II was the period to assess the sustainability of efficacy and long term safety.

During Study Period II, only patients who tolerated and agreed to continue osilodrostat treatment continued on the study. The patient was administered with the stable therapeutic dose which was achieved in the Study Period I.

Optional extension period (After Week-48): Patients who continued to receive clinical benefit, as assessed by the study Investigator and who wished to enter the extension period were reconsented at Week-48. Patients who entered the extension period continued to be treated with the study drug without interruption to be assessed for efficacy and safety. Patients who continued to benefit from study treatment as assessed by the study investigator and who completed Week-72 were offered to participate in a separate long-term safety follow-up study. The optional extension period ended after all patients had completed Week-72 or had discontinued early.

Post-treatment Follow-up: All patients had 30 days safety follow-up after the last dose of study treatment.

Study Design

Study Type:
Interventional
Actual Enrollment :
9 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Open-label, Dose Titration, Multi-center Study to Assess the Safety/Tolerability and Efficacy of Osilodrostat in Patients With All Types of Endogenous Cushing's Syndrome Except Cushing's Disease
Actual Study Start Date :
Sep 24, 2015
Actual Primary Completion Date :
Jun 7, 2018
Actual Study Completion Date :
Oct 29, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Osilodrostat

Patients in this arm took the study drug, osilodrostat.

Drug: Osilodrostat
Osirodrostat 1mg, 5mg & 10mg in the form of film-coated tablets was used for oral administration.
Other Names:
  • LCI699

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percent Change in the Mean Urine Free Cortisol (mUFC) at the Individual Level at Week 12 [Baseline, 12 weeks]

      Percent change from baseline in the mUFC at the individual patient level

    Secondary Outcome Measures

    1. Percent Change From Baseline in the mUFC at Individual Patient Level at Week 24 (Day 169) and Week 48 (Day 337) [Baseline, Week 24 (day 169) and Week 48 (day 337)]

      Percent change from baseline in the mUFC at the individual patient level

    2. Absolute Change From Baseline in the mUFC at Week 12 (Day 85), Week 24 (Day 169) and Week 48 (Day 337) [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change from baseline in the mUFC

    3. Percentage Change From Baseline in the mUFC at Week 12 (Day 85), Week 24 (Day 169) and Week 48 (Day 337) [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percent change from baseline in the mUFC

    4. Percentage of Participants With mUFC Response of Complete, Partial, and Overall Response [12, 24 and 48 weeks]

      Complete response rate = percentage of participants who had mUFC≤ ULN; Partial response rate = Percentage of participants who had mUFC>ULN and at least 50% reduction from baseline in mUFC. Overall response rate = Percentage of participants who had mUFC ≤ ULN or at least 50% reduction from baseline.

    5. Absolute Change From Baseline in Morning Serum Cortisol at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change from baseline in morning serum cortisol at the individual patient level

    6. Percentage Change From Baseline in Morning Serum Cortisol at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percentage change from baseline in morning serum cortisol at the individual patient level

    7. Absolute Change From Baseline in ACTH and Other Adrenal Steroid Hormones at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change from baseline in several steroid hormones at individual levels: ACTH, Serum 11-deoxycorticosterone, Aldosterone, Estradiol

    8. Percentage Change From Baseline in ACTH and Other Adrenal Steroid Hormones at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percent change from baseline in several steroid hormones at individual levels: ACTH, Serum 11-deoxycorticosterone, Aldosterone, Estradiol

    9. Absolute Change From Baseline in Other Adrenal Steroid Hormones at Individual Levels [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change from baseline in several steroid hormones at individual levels: Serum 11-deoxycortisol, Testosterone

    10. Percentage Change From Baseline in Other Adrenal Steroid Hormones at Individual Levels [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percent change from baseline in several steroid hormones at individual levels: Serum 11-deoxycortisol, Testosterone

    11. Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Fasting Glucose, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change in cardiovascular-related metabolic parameter fasting glucose, associated with Cushing's syndrome (CS)

    12. Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Fasting Glucose, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percentasge change in cardiovascular-related metabolic parameter fasting glucose, associated with Cushing's syndrome (CS)

    13. Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, HbA1c, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change in cardiovascular-related metabolic parameter HbA1c associated with Cushing's syndrome (CS)

    14. Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, HbA1c, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percentage change in cardiovascular-related metabolic parameter HbA1c associated with Cushing's syndrome (CS)

    15. Absolute Change From Baseline in Cardiovascular-related Metabolic Parameters, Cholesterol, HDL Cholesterol, LDL Cholesterol & Triglycerides, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change in cardiovascular-related metabolic parameters: cholesterol, HDL cholesterol, LDL cholesterol & triglycerides, associated with Cushing's syndrome (CS)

    16. Percentage Change From Baseline in Cardiovascular-related Metabolic Parameters, Cholesterol, HDL Cholesterol, LDL Cholesterol & Triglycerides, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percent change in cardiovascular-related metabolic parameters: cholesterol, HDL cholesterol, LDL cholesterol & triglycerides, associated with Cushing's syndrome (CS)

    17. Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, BMI, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change in cardiovascular-related metabolic parameter: BMI, associated with Cushing's syndrome (CS)

    18. Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, BMI, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percent change in cardiovascular-related metabolic parameter: BMI, associated with Cushing's syndrome (CS)

    19. Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Waist Circumference, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change in cardiovascular-related metabolic parameter: Waist circumference, associated with Cushing's syndrome (CS)

    20. Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Waist Circumference, at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percent change in cardiovascular-related metabolic parameter: Waist circumference, associated with Cushing's syndrome (CS)

    21. Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Sitting Blood Pressure (BP) at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Absolute change in cardiovascular-related metabolic parameter: sitting systolic BP & sitting diastolic BP, associated with Cushing's syndrome (CS)

    22. Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Sitting Blood Pressure (BP) at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      Percentage change in cardiovascular-related metabolic parameter: sitting systolic BP & sitting diastolic BP, associated with Cushing's syndrome

    23. Total Scores in Patient-Reported Outcomes Health-related Quality of Life (QoL) as Assessed by Cushing QoL at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      The Cushing's Disease Health-Related Quality of Life Questionnaire (Cushing QoL) (version 1.0) was developed to evaluate quality of life in patients with Cushing's syndrome (Webb et al 2008). The Cushing QoL is comprised of 12 items that capture patient responses on seven concepts: daily activities, healing and pain, mood and self-confidence, social concerns, physical appearance, memory and concern about the future. Each questionnaire of the Cushing QOL has a scale of 1-5 where '1' corresponding to 'Always' or 'Very much' and '5' to 'Never' or 'Not at all'. The lower the score, the greater the impact on HRQoL. The score is the sum of all the item response and can range from 12 (worst) to 60 points (best).

    24. Total Scores in Patient-Reported Outcomes Health-related Quality of Life (QoL) as Assessed by Beck Depression Inventory II (BDI-ll) Depression Score at Individual Level [Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)]

      The Beck Depression Inventory II (BDI-II) is a patient reported instrument that consists of 21 items designed to assess the intensity of depression in clinical & normal patients in the preceding two weeks. Each item is a list of four statements arranged in increasing severity about a particular symptom of depression. Each of 21 items corresponds to a symptom of depression and the sum of total score will be calculated where each item has a four-point scale ranging from 0 to 3, leading to a total score from zero to 63.

    25. Plasma Concentrations of Osilodrostat (LCI699) at Week 0 [Week 0]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    26. Plasma Concentrations of Osilodrostat (LCI699) at Week 1 [Week 1, 2 hours post-dose]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    27. Plasma Concentrations of Osilodrostat (LCI699) at Week 2 [Week 2]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    28. Plasma Concentrations of Osilodrostat (LCI699) at Week 3 [Week 3, 2 hours post-dose]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    29. Plasma Concentrations of Osilodrostat (LCI699) at Week 4 [Week 4, 2 hours post-dose]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    30. Plasma Concentrations of Osilodrostat (LCI699) at Week 6 [Week 6, 2 hours post-dose]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    31. Plasma Concentrations of Osilodrostat (LCI699) at Week 8 [Week 8, 2 hours post-dose]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    32. Plasma Concentrations of Osilodrostat (LCI699) at Week 10 [Week 10, 2 hours post-dose]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    33. Plasma Concentrations of Osilodrostat (LCI699) at Week 12 [Week 12]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    34. Plasma Concentrations of Osilodrostat (LCI699) at Week 16 [Week 16, 2 hours post-dose]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    35. Plasma Concentrations of Osilodrostat (LCI699) at Week 20 [Week 20, 2 hours post-dose]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    36. Plasma Concentrations of Osilodrostat (LCI699) at Week 24 [Week 24, 2 hours post-dose]

      Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients with confirmed Cushing's syndrome [i.e. ectopic corticotropin syndrome, adrenal adenoma, adrenal carcinoma, ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH), or Primary Pigmented Nodular Adrenal Dysplasia (PPNAD)]

    • For patients on medical treatment for hypercortisolism due to Cushing's syndrome, the washout periods had to be completed prior to baseline efficacy assessments

    Exclusion Criteria:

    • Patients with Cushing's disease

    • History of hypersensitivity to osilodrostat or to drugs of similar chemical classes

    • History of malignancy of any organ system, treated or untreated, within the past 5 years

    • Patients receiving treatment for within 4 weeks or ≤5 x half-life of the agent (whichever is longer) before first dose of osilodrostat

    • Patients with risk factors for QTc prolongation or Torsade de Pointes

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Fukushima city Fukushima Japan 960 1295
    2 Novartis Investigative Site Yokohama Kanagawa Japan 245-8575
    3 Novartis Investigative Site Sendai city Miyagi Japan 980 8574
    4 Novartis Investigative Site Chiba Japan 260 8677

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02468193
    Other Study ID Numbers:
    • CLCI699C1201
    First Posted:
    Jun 10, 2015
    Last Update Posted:
    May 6, 2020
    Last Verified:
    Apr 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Cushing's syndrome
    osilodrostat
    LCI699
    ectopic corticotropin syndrome
    adrenal adenoma
    adrenal carcinoma
    ACTH-Independent Macronodular Adrenal Hyperplasia
    AIMAH
    Primary Pigmented Nodular Adrenal Dysplasia
    PPNAD
    Additional relevant MeSH terms:
    Adenoma
    Adrenocortical Adenoma
    Adrenocortical Carcinoma
    ACTH Syndrome, Ectopic
    Cushing Syndrome
    Syndrome

    Study Results

    Participant Flow

    Recruitment Details Planned subjects: 10 subjects Actual enrolled: 9 subjects
    Pre-assignment Detail Planned subjects: 10 subjects
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Period Title: Overall Study
    STARTED 9
    Completed Week-12 (Study Period I) 7
    Discontinued at or Prior to Week-12 2
    Completed Week-12, Did Not Enter Per. II 3
    Completed Week-12, Entered Study Per. II 4
    Completed Week-48 (Study Period II) 2
    Discontinued at or Prior to Week48 2
    Compl. Wk-48, Didn't Enter Opt. Ext. Per 0
    Compl. Wk-48, Entered Opt. Ext. Period 2
    Completed Optional Extension Period 0
    Discontinued Study in Optional Ext. Per. 2
    COMPLETED 3
    NOT COMPLETED 6

    Baseline Characteristics

    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Overall Participants 9
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51.0
    (18.17)
    Sex: Female, Male (Count of Participants)
    Female
    7
    77.8%
    Male
    2
    22.2%
    Race/Ethnicity, Customized (participants) [Number]
    Japanese
    9
    100%
    Type of disease (Number) [Number]
    ACTH-Independent Macronodular Adrena;l Hyperplasia
    1
    11.1%
    Adrenal Adenoma
    5
    55.6%
    Ectopic Corticotropin Syndrome
    3
    33.3%

    Outcome Measures

    1. Primary Outcome
    Title Percent Change in the Mean Urine Free Cortisol (mUFC) at the Individual Level at Week 12
    Description Percent change from baseline in the mUFC at the individual patient level
    Time Frame Baseline, 12 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH- Patient 1 (n=1)
    -99.0
    Adrenal adenoma - Patient 1 (n=1)
    -97.8
    Adrenal adenoma - Patient 2 (n=1)
    -94.5
    Adrenal adenoma - Patient 3 (n=1)
    -91.5
    Adrenal adenoma - Patient 4 (n=1)
    -81.8
    Adrenal adenoma - Patient 5 (n=1)
    -52.6
    Ectopic corticotropin syndrome - Patient 1 (n=1)
    -99.0
    2. Secondary Outcome
    Title Percent Change From Baseline in the mUFC at Individual Patient Level at Week 24 (Day 169) and Week 48 (Day 337)
    Description Percent change from baseline in the mUFC at the individual patient level
    Time Frame Baseline, Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt) 1: Week (Wk) 24 (n=1)
    -99.5
    AIMAH-Patient 1:Wk 48 (n=1)
    -99.1
    Adrenal adenoma-Patient 2: Wk 24(n=1)
    -85.2
    Ectopic corticotropin syndrome-Pt 1: Wk 24(n=1)
    -91.6
    Ectopic corticotropin syndrome-Pt 1: Wk 48(n=1)
    -91.0
    3. Secondary Outcome
    Title Absolute Change From Baseline in the mUFC at Week 12 (Day 85), Week 24 (Day 169) and Week 48 (Day 337)
    Description Absolute change from baseline in the mUFC
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    Week 12 (day 85)( n = 7)
    -422.10
    Week 24 (day 169) (n = 3)
    -7428.10
    Week 48 (day 337) (n = 2)
    -8521.00
    4. Secondary Outcome
    Title Percentage Change From Baseline in the mUFC at Week 12 (Day 85), Week 24 (Day 169) and Week 48 (Day 337)
    Description Percent change from baseline in the mUFC
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    Week 12 (day 85)( n = 7)
    -94.47
    Week 24 (day 169) (n = 3)
    -91.57
    Week 48 (day 337) (n = 2)
    -95.04
    5. Secondary Outcome
    Title Percentage of Participants With mUFC Response of Complete, Partial, and Overall Response
    Description Complete response rate = percentage of participants who had mUFC≤ ULN; Partial response rate = Percentage of participants who had mUFC>ULN and at least 50% reduction from baseline in mUFC. Overall response rate = Percentage of participants who had mUFC ≤ ULN or at least 50% reduction from baseline.
    Time Frame 12, 24 and 48 weeks

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 9
    Week 12: Complete responders
    66.7
    741.1%
    Week 12: Partial responders
    11.1
    123.3%
    Week 12: Overall responders
    77.8
    864.4%
    Week 24: Complete responders (n =3)
    66.7
    741.1%
    Week 24: Partial responders (n = 3)
    33.3
    370%
    Week 24: Overall responders (n = 3)
    100
    1111.1%
    Week 48: Complete responders (n = 2)
    50.0
    555.6%
    Week 48: Partial responders (n = 2)
    50.0
    555.6%
    Week 48: Overall responders (n = 2)
    100
    1111.1%
    6. Secondary Outcome
    Title Absolute Change From Baseline in Morning Serum Cortisol at Individual Level
    Description Absolute change from baseline in morning serum cortisol at the individual patient level
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt) 1: Week (Wk) 12 (n = 1)
    -607
    AIMAH-Patient 1: Wk 24 (n = 1)
    -571
    AIMAH-Patient 1: Wk 48 (n = 1)
    -580
    Adrenal adenoma-Patient 1: Wk 12 (n =1)
    -334
    Adrenal adenoma-Patient 2: Wk 12(n =1)
    -157
    Adrenal adenoma-Patient 2: Wk 24 (n =1)
    -135
    Adrenal adenoma-Patient 3: Wk 12 (n =1)
    -300
    Adrenal adenoma-Patient 4: Wk 12 (n =1)
    -30
    Adrenal adenoma-Patient 5: Wk 12 (n =1)
    -13
    Ectopic corticotropin syndrome-Pt 1: Wk 12 (n =1)
    -949
    Ectopic corticotropin syndrome-Pt 1: Wk24 (n=1)
    -927
    Ectopic corticotropin syndrome-Pt 1: Wk48 (n=1)
    -861
    7. Secondary Outcome
    Title Percentage Change From Baseline in Morning Serum Cortisol at Individual Level
    Description Percentage change from baseline in morning serum cortisol at the individual patient level
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt) 1: Week (Wk) 12 (n = 1)
    -73.3
    AIMAH-Patient 1: Wk 24 (n = 1)
    -69.0
    AIMAH-Patient 1: Wk 48 (n = 1)
    -70.0
    Adrenal adenoma-Patient 1: Wk 12 (n =1)
    -78.0
    Adrenal adenoma-Patient 2: Wk 12(n =1)
    -50.8
    Adrenal adenoma-Patient 2: Wk 24 (n =1)
    -43.7
    Adrenal adenoma-Patient 3: Wk 12 (n =1)
    -56.1
    Adrenal adenoma-Patient 4: Wk 12 (n =1)
    -8.7
    Adrenal adenoma-Patient 5: Wk 12 (n =1)
    -3.5
    Ectopic corticotropin syndrome-Pt 1: Wk 12 (n =1)
    -71.4
    Ectopic corticotropin syndrome-Pt 1: Wk24 (n=1)
    -69.7
    Ectopic corticotropin syndrome-Pt 1: Wk48 (n=1)
    -64.7
    8. Secondary Outcome
    Title Absolute Change From Baseline in ACTH and Other Adrenal Steroid Hormones at Individual Level
    Description Absolute change from baseline in several steroid hormones at individual levels: ACTH, Serum 11-deoxycorticosterone, Aldosterone, Estradiol
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title ACTH Serum 11-deoxycorticosterone Aldosterone Estradiol
    Arm/Group Description Adrenocorticotropic hormone adrenal steroid hormones: Serum 11-deoxycorticosterone adrenal steroid hormones: Aldosterone adrenal steroid hormones: Estradiol
    Measure Participants 7 7 7 7
    AIMAH-Patient (Pt) 1 Wk 12 (n=1,1,1,1)
    0
    2179
    52
    705
    AIMAH-Pt 1 Wk 24 (n=1,1,1,1)
    0
    3601
    236
    235
    AIMAH-Pt 1 Wk 48 (n=1,1,1,1)
    0
    454
    170
    400
    Adrenal adenoma-Pt 1 Wk 12 (n=1,1,1,1)
    1.1
    2966
    -27
    -404
    Adrenal adenoma-Pt 2 Wk 12 (n=1,1,1,1)
    0
    5145
    -981
    4
    Adrenal adenoma-Pt 2 Wk 24(n=1,1,1,1)
    0
    0
    450
    -4
    Adrenal adenoma-Pt 3 Wk 12 (n=1,1,1,1)
    0
    0
    -147
    77
    Adrenal adenoma-Pt 4 Wk 12 (n=1,1,1,1)
    0
    787
    3
    18
    Adrenal adenoma-Pt 5 Wk 12 (n=1,1,1,1)
    0
    0
    0
    -11
    Ectopic ACTH syndrome-Pt 1: Wk 12 (n=1,1,1,1)
    -67.7
    -696
    145
    51
    Ectopic ACTH syndrome-Pt 1: Wk 24 (n=1,1,1,1)
    -47.3
    -91
    40
    -11
    Ectopic ACTH syndrome-Pt 1: Wk 48 (n=1,1,1,1)
    13.3
    -91
    37
    11
    9. Secondary Outcome
    Title Percentage Change From Baseline in ACTH and Other Adrenal Steroid Hormones at Individual Level
    Description Percent change from baseline in several steroid hormones at individual levels: ACTH, Serum 11-deoxycorticosterone, Aldosterone, Estradiol
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title ACTH Serum 11-deoxycorticosterone Aldosterone Estradiol
    Arm/Group Description Adrenocorticotropic hormone adrenal steroid hormones: Serum 11-deoxycorticosterone adrenal steroid hormones: Aldosterone adrenal steroid hormones: Estradiol
    Measure Participants 7 7 7 7
    AIMAH-Patient (Pt) 1 Wk 12 (n =0,1,0,1)
    118.0
    1282
    AIMAH-Pt 1 Wk 24 (n=0,1,0,1)
    195.1
    427.3
    AIMAH-Pt 1 Wk 48 (n=0,1,0,1)
    24.6
    727.3
    Adrenal adenoma-Pt 1 Wk 12 (n =0,0,1,1)
    -13.9
    -53.7
    Adrenal adenoma-Pt 2 Wk 12 (n =0,0,1,1)
    -100
    1.9
    Adrenal adenoma-Pt 2 Wk 24 (n =0,0,1,1)
    45.9
    -1.9
    Adrenal adenoma-Pt 3 Wk 12 (n =0,0,1,1)
    -75.0
    513.3
    Adrenal adenoma-Pt 4 Wk 12 (n =0,0,1,1)
    10.0
    120.0
    Adrenal adenoma-Pt 5 Wk 12 (n =0,0,0,1)
    -100
    Ectopic ACTH syndrome-Pt 1: Wk 12 (n=1,1,0,1)
    -71.6
    -100
    72.9
    Ectopic ACTH syndrome-Pt 1: Wk 24 (n=1,1,0,1)
    -50.0
    -13.1
    -15.7
    Ectopic ACTH syndrome-Pt 1: Wk 48 (n=1,1,0,1)
    14.1
    -13.1
    15.7
    10. Secondary Outcome
    Title Absolute Change From Baseline in Other Adrenal Steroid Hormones at Individual Levels
    Description Absolute change from baseline in several steroid hormones at individual levels: Serum 11-deoxycortisol, Testosterone
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Serum 11-deoxycortisol Testosterone
    Arm/Group Description adrenal steroid hormones: Serum 11-deoxycortisol adrenal steroid hormones: Testosterone
    Measure Participants 7 7
    AIMAH-Patient (Pt) 1 Wk 12 (n = 1,1)
    -4.35
    0.76
    AIMAH-Pt 1 Wk 24 (n = 1,1)
    -8.5
    0.66
    AIMAH-Pt 1 Wk 48 (n = 1,1)
    -15.54
    -0.03
    Adrenal adenoma-Pt 1 Wk 12 (n = 1,1)
    6.91
    0.31
    Adrenal adenoma-Pt 2 Wk 12 (n = 1,1)
    2.81
    0.11
    Adrenal adenoma-Pt 2 Wk 24 (n = 1,1)
    -0.64
    -0.35
    Adrenal adenoma-Pt 3 Wk 12 (n = 1,1)
    7.34
    0.42
    Adrenal adenoma-Pt 4 Wk 12 (n = 1,1)
    3.5
    0.03
    Adrenal adenoma-Pt 5 Wk 12 (n = 1,1)
    -1.39
    0
    Ectopic ACTH syndrome-Pt 1 Wk 12(n = 1,1)
    -15.81
    5.83
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n = 1,1)
    -12.41
    -2.71
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n = 1,1)
    -2.52
    -2.01
    11. Secondary Outcome
    Title Percentage Change From Baseline in Other Adrenal Steroid Hormones at Individual Levels
    Description Percent change from baseline in several steroid hormones at individual levels: Serum 11-deoxycortisol, Testosterone
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Serum 11-deoxycortisol Testosterone
    Arm/Group Description adrenal steroid hormones: Serum 11-deoxycortisol adrenal steroid hormones: Testosterone
    Measure Participants 7 7
    AIMAH-Patient (Pt) 1 Wk 12 (n=1, 1)
    -17.8
    73.1
    AIMAH-Pt 1 Wk 24 (n=1, 1)
    -34.9
    63.5
    AIMAH-Pt 1 Wk 48 (n=1, 1)
    -63.7
    -2.9
    Adrenal adenoma-Pt 1 Wk 12 (n=1,1)
    143.7
    100.0
    Adrenal adenoma-Pt 2 Wk 12 (n=1,1)
    108.9
    10.6
    Adrenal adenoma-Pt 2 Wk 24 (n=1,1)
    -24.8
    -33.7
    Adrenal adenoma-Pt 3 Wk 12 (n=1, 1)
    127.2
    93.3
    Adrenal adenoma-Pt 4 Wk 12 (n=1, 1)
    267.2
    14.3
    Adrenal adenoma-Pt 5 Wk 12 (n=1,1)
    -43.2
    0.0
    Ectopic ACTH syndrome-Pt 1 Wk 12 (n=1, 1)
    -64.8
    96.5
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n=1, 1)
    -50.9
    -44.9
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n=1, 1)
    -10.3
    -33.3
    12. Secondary Outcome
    Title Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Fasting Glucose, at Individual Level
    Description Absolute change in cardiovascular-related metabolic parameter fasting glucose, associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt) 1 Wk 12 (n =1)
    -0.78
    AIMAH-Patient (Pt) 1 Wk 24 (n =1)
    -0.84
    AIMAH-Patient (Pt) 1 Wk 48 (n =1)
    -0.78
    Adrenal adenoma-Pt 1 Wk 12 (n =1)
    1.22
    Adrenal adenoma-Pt 2 Wk 12 (n =1)
    -1.89
    Adrenal adenoma-Pt 2 Wk 24 (n =1)
    0.22
    Adrenal adenoma-Pt 3 Wk 12 (n =1)
    -0.28
    Adrenal adenoma-Pt 4 Wk 12 (n =1)
    -0.67
    Adrenal adenoma-Pt 5 Wk 12 (n =1)
    -0.05
    Ectopic ACTH syndrome-Pt 1 Wk 12 (n =1)
    -0.33
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n =1)
    -0.39
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n =1)
    0.06
    13. Secondary Outcome
    Title Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Fasting Glucose, at Individual Level
    Description Percentasge change in cardiovascular-related metabolic parameter fasting glucose, associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt) 1 Wk 12 (n =1)
    -15.3
    AIMAH-Patient (Pt) 1 Wk 24 (n =1)
    -16.4
    AIMAH-Patient (Pt) 1 Wk 48 (n =1)
    -15.3
    Adrenal adenoma-Pt 1 Wk 12 (n =1)
    24.2
    Adrenal adenoma-Pt 2 Wk 12 (n =1)
    -27.2
    Adrenal adenoma-Pt 2 Wk 24 (n =1)
    3.2
    Adrenal adenoma-Pt 3 Wk 12 (n =1)
    -5.0
    Adrenal adenoma-Pt 4 Wk 12 (n =1)
    -11.3
    Adrenal adenoma-Pt 5 Wk 12 (n =1)
    -0.9
    Ectopic ACTH syndrome-Pt 1 Wk 12 (n =1)
    -5.9
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n =1)
    -7.0
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n =1)
    1.1
    14. Secondary Outcome
    Title Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, HbA1c, at Individual Level
    Description Absolute change in cardiovascular-related metabolic parameter HbA1c associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt) 1 Wk 12 (n=1)
    -0.1
    AIMAH-Pt 1 Wk 24 (n=1)
    -0.1
    AIMAH-Pt 1 Wk 48 (n=1)
    -0.2
    Adrenal adenoma-Pt 1 Wk 12 (n=1)
    0.3
    Adrenal adenoma-Pt 2 Wk 12 (n=1)
    -0.4
    Adrenal adenoma-Pt 2 Wk 24 (n=1)
    -0.7
    Adrenal adenoma-Pt 3 Wk 12 (n=1)
    -1.4
    Adrenal adenoma-Pt 4 Wk 12 (n=1)
    -0.9
    Adrenal adenoma-Pt 5 Wk 12 (n=1)
    -0.1
    Ectopic ACTH syndrome-Pt 1 Wk 12 (n=1)
    0.3
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n=1)
    0.5
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n=1)
    0.8
    15. Secondary Outcome
    Title Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, HbA1c, at Individual Level
    Description Percentage change in cardiovascular-related metabolic parameter HbA1c associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt) 1 Wk 12 (n=1)
    -1.8
    AIMAH-Pt 1 Wk 24 (n=1)
    -1.8
    AIMAH-Pt 1 Wk 48 (n=1)
    -3.6
    Adrenal adenoma-Pt 1 Wk 12 (n=1)
    6.2
    Adrenal adenoma-Pt 2 Wk 12 (n=1)
    -6.5
    Adrenal adenoma-Pt 2 Wk 24 (n=1)
    -11.3
    Adrenal adenoma-Pt 3 Wk 12 (n=1)
    -20.3
    Adrenal adenoma-Pt 4 Wk 12 (n=1)
    -12.2
    Adrenal adenoma-Pt 5 Wk 12 (n=1)
    -1.5
    Ectopic ACTH syndrome-Pt 1 Wk 12 (n=1)
    5.4
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n=1)
    8.9
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n=1)
    14.3
    16. Secondary Outcome
    Title Absolute Change From Baseline in Cardiovascular-related Metabolic Parameters, Cholesterol, HDL Cholesterol, LDL Cholesterol & Triglycerides, at Individual Level
    Description Absolute change in cardiovascular-related metabolic parameters: cholesterol, HDL cholesterol, LDL cholesterol & triglycerides, associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Cholesterol HDL Cholesterol LDL Cholesterol Triglycerides
    Arm/Group Description Patients in this arm took the study drug, osilodrostat. Patients in this arm took the study drug, osilodrostat. Patients in this arm took the study drug, osilodrostat. Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7 7 7 7
    AIMAH-Patient (Pt) 1 Wk 12 (n =1,1,1,1)
    -0.67
    -0.85
    0.21
    -0.87
    AIMAH-Pt 1 Wk 24 (n =1,1,1,1)
    -0.65
    -1.01
    0.18
    -0.64
    AIMAH-Pt 1 Wk 48 (n =1,1,1,1)
    -0.72
    -0.57
    -0.08
    -0.76
    Adrenal adenoma-Pt 1 Wk 12 (n =1,1,1,1)
    -1.56
    -0.26
    -1.11
    -1.42
    Adrenal adenoma-Pt 2 Wk 12 (n =1,1,1,1)
    -0.54
    -0.64
    -0.26
    0.11
    Adrenal adenoma-Pt 2 Wk 24 (n =1,1,1,1)
    0.26
    -0.33
    0.31
    0.08
    Adrenal adenoma-Pt 3 Wk 12 (n =1,1,1,1)
    -0.55
    -0.16
    -0.19
    -1.36
    Adrenal adenoma-Pt 4 Wk 12 (n =1,1,1,1)
    1.09
    0.18
    0.72
    0.58
    Adrenal adenoma-Pt 5 Wk 12 (n =1,1,1,1)
    -0.39
    -0.21
    -0.18
    0.44
    Ectopic ACTH syndrome-Pt 1 Wk 12(n =1,1,1,1)
    -0.16
    0.16
    -0.11
    -0.47
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n =1,1,1,1)
    -0.26
    0.49
    -0.29
    -0.83
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n =1,1,1,1)
    -0.08
    0.29
    -0.31
    0.22
    17. Secondary Outcome
    Title Percentage Change From Baseline in Cardiovascular-related Metabolic Parameters, Cholesterol, HDL Cholesterol, LDL Cholesterol & Triglycerides, at Individual Level
    Description Percent change in cardiovascular-related metabolic parameters: cholesterol, HDL cholesterol, LDL cholesterol & triglycerides, associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Cholesterol HDL Cholesterol LDL Cholesterol Triglycerides
    Arm/Group Description Patients in this arm took the study drug, osilodrostat. Patients in this arm took the study drug, osilodrostat. Patients in this arm took the study drug, osilodrostat. Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7 7 7 7
    AIMAH-Patient (Pt) 1 Wk 12 (n =1,1,1,1)
    -11.1
    -33.2
    6.3
    -49.4
    AIMAH-Pt 1 Wk 24 (n =1,1,1,1)
    -10.7
    -39.5
    5.4
    -36.4
    AIMAH-Pt 1 Wk 48 (n =1,1,1,1)
    -11.9
    -22.3
    -2.4
    -43.2
    Adrenal adenoma-Pt 1 Wk 12 (n =1,1,1,1)
    -23.0
    -27.1
    -24.9
    -28.8
    Adrenal adenoma-Pt 2 Wk 12 (n =1,1,1,1)
    -11.9
    -34.4
    -10.6
    12.5
    Adrenal adenoma-Pt 2 Wk 24 (n =1,1,1,1)
    5.7
    -17.7
    12.6
    9.1
    Adrenal adenoma-Pt 3 Wk 12 (n =1,1,1,1)
    -9.5
    -9.4
    -5.5
    -56.7
    Adrenal adenoma-Pt 4 Wk 12 (n =1,1,1,1)
    23.0
    15.5
    26.5
    46.8
    Adrenal adenoma-Pt 5 Wk 12 (n =1,1,1,1)
    -8.7
    -11.4
    -9.3
    33.3
    Ectopic ACTH syndrome-Pt 1 Wk 12(n =1,1,1,1)
    -3.8
    12.4
    -4.5
    -32.0
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n =1,1,1,1)
    -6.2
    38.0
    -11.8
    -56.5
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n =1,1,1,1)
    -1.9
    22.5
    -12.6
    15.0
    18. Secondary Outcome
    Title Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, BMI, at Individual Level
    Description Absolute change in cardiovascular-related metabolic parameter: BMI, associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt) 1 Wk 12 (n =1)
    -0.5
    AIMAH-Pt 1 Wk 24 (n =1)
    -2.3
    AIMAH-Pt 1 Wk 48 (n =1)
    -1.6
    Adrenal adenoma-Pt 1 Wk 12 (n =1)
    0.6
    Adrenal adenoma-Pt 2 Wk 12 (n =1)
    -1.2
    Adrenal adenoma-Pt 2 Wk 24 (n =1)
    -3.6
    Adrenal adenoma-Pt 3 Wk 12 (n =1)
    0.7
    Adrenal adenoma-Pt 4 Wk 12 (n =1)
    0.2
    Adrenal adenoma-Pt 5 Wk 12 (n =1)
    0.1
    Ectopic ACTH syndrome-Pt 1 Wk 12(n =1)
    1.8
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n =1)
    3.0
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n =1)
    3.6
    19. Secondary Outcome
    Title Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, BMI, at Individual Level
    Description Percent change in cardiovascular-related metabolic parameter: BMI, associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt) 1 Wk 12 (n =1)
    -2.1
    AIMAH-Pt 1 Wk 24 (n =1)
    -9.6
    AIMAH-Pt 1 Wk 48 (n =1)
    -6.7
    Adrenal adenoma-Pt 1 Wk 12 (n =1)
    1.9
    Adrenal adenoma-Pt 2 Wk 12 (n =1)
    -3.1
    Adrenal adenoma-Pt 2 Wk 24 (n =1)
    -9.4
    Adrenal adenoma-Pt 3 Wk 12 (n =1)
    3.3
    Adrenal adenoma-Pt 4 Wk 12 (n =1)
    0.9
    Adrenal adenoma-Pt 5 Wk 12 (n =1)
    0.5
    Ectopic ACTH syndrome-Pt 1 Wk 12(n =1)
    7.4
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n =1)
    12.3
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n =1)
    14.8
    20. Secondary Outcome
    Title Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Waist Circumference, at Individual Level
    Description Absolute change in cardiovascular-related metabolic parameter: Waist circumference, associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt)1 Wk 12 (n=1)
    -2.0
    AIMAH-Pt1 Wk 24 (n=1)
    -7.5
    AIMAH-Pt1 Wk 48 (n=1)
    -5.5
    Adrenal adenoma-Pt 1 Wk 12 (n=1)
    -2.0
    Adrenal adenoma-Pt 2 Wk 12 (n=1)
    -1.0
    Adrenal adenoma-Pt 2 Wk 24 (n=1)
    -8.0
    Adrenal adenoma-Pt 3 Wk 12 (n=1)
    -4.0
    Adrenal adenoma-Pt 4 Wk 12 (n=1)
    1.0
    Adrenal adenoma-Pt 5 Wk 12 (n=1)
    -0.3
    Ectopic ACTH syndrome-Pt 1 Wk 12 (n=1)
    2.5
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n=1)
    11.0
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n=1)
    9.5
    21. Secondary Outcome
    Title Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Waist Circumference, at Individual Level
    Description Percent change in cardiovascular-related metabolic parameter: Waist circumference, associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient (Pt)1 Wk 12 (n=1)
    -2.4
    AIMAH-Pt1 Wk 24 (n=1)
    -9.0
    AIMAH-Pt1 Wk 48 (n=1)
    -6.6
    Adrenal adenoma-Pt 1 Wk 12 (n=1)
    -1.8
    Adrenal adenoma-Pt 2 Wk 12 (n=1)
    -0.9
    Adrenal adenoma-Pt 2 Wk 24 (n=1)
    -7.1
    Adrenal adenoma-Pt 3 Wk 12 (n=1)
    -4.9
    Adrenal adenoma-Pt 4 Wk 12 (n=1)
    1.1
    Adrenal adenoma-Pt 5 Wk 12 (n=1)
    -0.4
    Ectopic ACTH syndrome-Pt 1 Wk 12 (n=1)
    2.9
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n=1)
    12.9
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n=1)
    11.1
    22. Secondary Outcome
    Title Absolute Change From Baseline in Cardiovascular-related Metabolic Parameter, Sitting Blood Pressure (BP) at Individual Level
    Description Absolute change in cardiovascular-related metabolic parameter: sitting systolic BP & sitting diastolic BP, associated with Cushing's syndrome (CS)
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Sitting Systolic BP Sitting Diastolic BP
    Arm/Group Description Patients in this arm took the study drug, osilodrostat. Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7 7
    AIMAH-Patient (Pt) 1Wk 12 (n =1, 1)
    -44.3
    -31.0
    AIMAH-Patient (Pt) 1 Wk 24 (n =1, 1)
    -48.34
    -32.66
    AIMAH-Patient (Pt) 1 Wk 48 (n =1, 1)
    -40.34
    -19.0
    Adrenal adenoma-Pt 1 Wk 12 (n=1,1)
    11.67
    -3.67
    Adrenal adenoma-Pt 2 Wk 12 (n=1,1)
    -50.67
    -37.0
    Adrenal adenoma-Pt 2 Wk 24 (n=1,1)
    -32.33
    -26.66
    Adrenal adenoma-Pt 3 Wk 12 (n=1,1)
    -16.0
    -6.67
    Adrenal adenoma-Pt 4 Wk 12 (n=1,1)
    -6.67
    7.33
    Adrenal adenoma-Pt 5 Wk 12 (n=1,1)
    11.0
    3.33
    Ectopic ACTH syndrome-Pt 1 Wk 12(n=1,1)
    -17.67
    -13.67
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n=1,1)
    4.33
    4.0
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n=1,1)
    -1.0
    -0.67
    23. Secondary Outcome
    Title Percentage Change From Baseline in Cardiovascular-related Metabolic Parameter, Sitting Blood Pressure (BP) at Individual Level
    Description Percentage change in cardiovascular-related metabolic parameter: sitting systolic BP & sitting diastolic BP, associated with Cushing's syndrome
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Sitting Systolic BP Sitting Diastolic BP
    Arm/Group Description Patients in this arm took the study drug, osilodrostat. Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7 7
    AIMAH-Patient (Pt) 1Wk 12 (n =1, 1)
    -31.1
    -32.5
    AIMAH-Patient (Pt) 1 Wk 24 (n =1, 1)
    -33.9
    -34.3
    AIMAH-Patient (Pt) 1 Wk 48 (n =1, 1)
    -28.3
    -19.9
    Adrenal adenoma-Pt 1 Wk 12 (n=1,1)
    9.2
    -4.1
    Adrenal adenoma-Pt 2 Wk 12 (n=1,1)
    -31.3
    -33.2
    Adrenal adenoma-Pt 2 Wk 24 (n=1,1)
    -20.0
    -23.9
    Adrenal adenoma-Pt 3 Wk 12 (n=1,1)
    -12.3
    -8.9
    Adrenal adenoma-Pt 4 Wk 12 (n=1,1)
    -4.3
    9.9
    Adrenal adenoma-Pt 5 Wk 12 (n=1,1)
    9.3
    5.1
    Ectopic ACTH syndrome-Pt 1 Wk 12(n=1,1)
    -14.1
    -16.5
    Ectopic ACTH syndrome-Pt 1 Wk 24 (n=1,1)
    3.4
    4.8
    Ectopic ACTH syndrome-Pt 1 Wk 48 (n=1,1)
    -0.8
    -0.8
    24. Secondary Outcome
    Title Total Scores in Patient-Reported Outcomes Health-related Quality of Life (QoL) as Assessed by Cushing QoL at Individual Level
    Description The Cushing's Disease Health-Related Quality of Life Questionnaire (Cushing QoL) (version 1.0) was developed to evaluate quality of life in patients with Cushing's syndrome (Webb et al 2008). The Cushing QoL is comprised of 12 items that capture patient responses on seven concepts: daily activities, healing and pain, mood and self-confidence, social concerns, physical appearance, memory and concern about the future. Each questionnaire of the Cushing QOL has a scale of 1-5 where '1' corresponding to 'Always' or 'Very much' and '5' to 'Never' or 'Not at all'. The lower the score, the greater the impact on HRQoL. The score is the sum of all the item response and can range from 12 (worst) to 60 points (best).
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient 1: Week (Wk) 12 (n=1)
    48
    AIMAH-Patient 1: Wk 24 (n=1)
    51
    AIMAH-Patient 1: Wk 48 (n=1)
    47
    Adrenal adenoma-Patient 1: Wk 12(n=1)
    29
    Adrenal adenoma-Patient 2: Wk 12(n=1)
    18
    Adrenal adenoma-Patient 2: Wk 24 (n = 1)
    22
    Adrenal adenoma-Patient 3: Wk 12 (n =1)
    29
    Adrenal adenoma-Patient 4: Wk 12 (n =1)
    38
    Adrenal adenoma-Patient 5: Wk 12 (n=1)
    45
    Ectopic corticotropin syndrome-Pt 1: Wk 12 (n =1)
    31
    Ectopic corticotropin syndrome-Pt 1: Wk 24 (n =1)
    33
    Ectopic corticotropin syndrome-Pt 1: Wk 48 (n =1)
    23
    25. Secondary Outcome
    Title Total Scores in Patient-Reported Outcomes Health-related Quality of Life (QoL) as Assessed by Beck Depression Inventory II (BDI-ll) Depression Score at Individual Level
    Description The Beck Depression Inventory II (BDI-II) is a patient reported instrument that consists of 21 items designed to assess the intensity of depression in clinical & normal patients in the preceding two weeks. Each item is a list of four statements arranged in increasing severity about a particular symptom of depression. Each of 21 items corresponds to a symptom of depression and the sum of total score will be calculated where each item has a four-point scale ranging from 0 to 3, leading to a total score from zero to 63.
    Time Frame Baseline, Week 12 (day 85), Week 24 (day 169) and Week 48 (day 337)

    Outcome Measure Data

    Analysis Population Description
    Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    Measure Participants 7
    AIMAH-Patient 1: Week (Wk) 12 (n =1)
    4
    AIMAH-Patient 1: Wk 24 (n =1)
    15
    AIMAH-Patient 1: Wk 48 (n =1)
    12
    Adrenal adenoma-Patient 1: Wk 12 (n =1)
    33
    Adrenal adenoma-Patient 2: Wk 12 (n =1)
    35
    Adrenal adenoma-Patient 2: Wk 24 (n =1)
    37
    Adrenal adenoma-Patient 3: Wk 12 (n =1)
    30
    Adrenal adenoma-Patient 4: Wk 12 (n =1)
    26
    Adrenal adenoma-Patient 5: Wk 12 (n =1)
    10
    Ectopic corticotropin syndrome-Pt 1: Wk 12 (n =1)
    9
    Ectopic corticotropin syndrome-Pt 1: Wk 24 (n =1)
    10
    Ectopic corticotropin syndrome-Pt 1: Wk 48 (n =1)
    22
    26. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 0
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 0

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 1 8 0 0
    Week 0: 0.75 hour post-dose
    0.971
    (NA)
    0.405
    (0.673)
    Week 0: 2 hours post-dose
    5.11
    (NA)
    5.29
    (4.94)
    Week 0: 4 hours post-dose
    3.77
    (NA)
    8.12
    (2.36)
    27. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 1
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 1, 2 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 1 5 1 2
    Mean (Standard Deviation) [ng/mL]
    10.9
    (NA)
    10.5
    (6.57)
    21.3
    (NA)
    22.3
    (14.2)
    28. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 2
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 2

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 2 2 2 2
    Week 2: 0.75 hour post-dose
    3.89
    (2.76)
    3.69
    (3.3)
    33.1
    (19.2)
    34.9
    (34.6)
    Week 2: 2 hours post-dose
    8.93
    (2.36)
    14.3
    (7.64)
    21.3
    (4.53)
    33.6
    (8.84)
    Week 2: 4 hours post-dose
    7.01
    (2.69)
    11.1
    (NA)
    13.6
    (3.89)
    29.2
    (0.354)
    29. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 3
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 3, 2 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 4 1 1 2
    Mean (Standard Deviation) [ng/mL]
    7.09
    (2.07)
    7.62
    (NA)
    23.2
    (NA)
    37.8
    (0.849)
    30. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 4
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 4, 2 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 4 2 0 2
    Mean (Standard Deviation) [ng/mL]
    4.08
    (2.61)
    9.91
    (3.53)
    24.0
    (21.00)
    31. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 6
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 6, 2 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 4 2 0 1
    Mean (Standard Deviation) [ng/mL]
    6.74
    (2.42)
    12.7
    (9.08)
    31.7
    (NA)
    32. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 8
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 8, 2 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 5 1 0 0
    Mean (Standard Deviation) [ng/mL]
    3.35
    (2.75)
    13.9
    (NA)
    33. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 10
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 10, 2 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 4 2 0 0
    Mean (Standard Deviation) [ng/mL]
    4.73
    (1.26)
    11.3
    (4.57)
    34. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 12
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 12

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 2 1 0 0
    Week 12: 0.75 hour post-dose
    0.382
    (0.171)
    3.1
    (NA)
    Week 12: 2 hours post-dose
    4.62
    (2.51)
    9.98
    (NA)
    Week 12: 4 hours post-dose
    3.58
    (2.3)
    6.57
    (NA)
    35. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 16
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 16, 2 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 2 0 0 0
    Mean (Standard Deviation) [ng/mL]
    5.71
    (1.33)
    36. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 20
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 20, 2 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 1 0 0 0
    Mean (Standard Deviation) [ng/mL]
    0.794
    (NA)
    37. Secondary Outcome
    Title Plasma Concentrations of Osilodrostat (LCI699) at Week 24
    Description Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.
    Time Frame Week 24, 2 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analysis set (PAS): Consisted of all patients who received at least one dose of osilodrostat and had at least one evaluable PK concentration at any visit (post-first-dose).
    Arm/Group Title Osilodrostat 1mg Osilodrostat 2mg Osilodrostat 3mg Osilodrostat 5mg
    Arm/Group Description Patients in this arm took 1mg of study drug, osilodrostat. Patients in this arm took 2mg of study drug, osilodrostat. Patients in this arm took 3mg of study drug, osilodrostat. Patients in this arm took 5mg of study drug, osilodrostat.
    Measure Participants 2 0 0 0
    Mean (Standard Deviation) [ng/mL]
    6.51
    (2.14)

    Adverse Events

    Time Frame Adverse events (AEs) were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 68.0 weeks.
    Adverse Event Reporting Description AE description; Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
    Arm/Group Title Osilodrostat
    Arm/Group Description Patients in this arm took the study drug, osilodrostat.
    All Cause Mortality
    Osilodrostat
    Affected / at Risk (%) # Events
    Total 0/9 (0%)
    Serious Adverse Events
    Osilodrostat
    Affected / at Risk (%) # Events
    Total 4/9 (44.4%)
    Cardiac disorders
    Myocardial infarction 1/9 (11.1%)
    Endocrine disorders
    Adrenal insufficiency 2/9 (22.2%)
    Infections and infestations
    Pneumonia 1/9 (11.1%)
    Psychiatric disorders
    Psychiatric symptom 1/9 (11.1%)
    Other (Not Including Serious) Adverse Events
    Osilodrostat
    Affected / at Risk (%) # Events
    Total 9/9 (100%)
    Blood and lymphatic system disorders
    Iron deficiency anaemia 1/9 (11.1%)
    Ear and labyrinth disorders
    Vertigo 1/9 (11.1%)
    Endocrine disorders
    Adrenal insufficiency 5/9 (55.6%)
    Steroid withdrawal syndrome 1/9 (11.1%)
    Gastrointestinal disorders
    Abdominal distension 1/9 (11.1%)
    Abdominal pain upper 1/9 (11.1%)
    Constipation 2/9 (22.2%)
    Dental caries 1/9 (11.1%)
    Enterocolitis 1/9 (11.1%)
    Stomatitis 1/9 (11.1%)
    General disorders
    Malaise 3/9 (33.3%)
    Oedema peripheral 1/9 (11.1%)
    Pyrexia 1/9 (11.1%)
    Hepatobiliary disorders
    Primary biliary cholangitis 1/9 (11.1%)
    Infections and infestations
    Cellulitis 1/9 (11.1%)
    Nasopharyngitis 3/9 (33.3%)
    Osteomyelitis 1/9 (11.1%)
    Injury, poisoning and procedural complications
    Rib fracture 1/9 (11.1%)
    Investigations
    Alanine aminotransferase increased 2/9 (22.2%)
    Amylase increased 1/9 (11.1%)
    Aspartate aminotransferase increased 2/9 (22.2%)
    Blood alkaline phosphatase increased 2/9 (22.2%)
    Gamma-glutamyltransferase increased 3/9 (33.3%)
    Weight decreased 1/9 (11.1%)
    Weight increased 1/9 (11.1%)
    Metabolism and nutrition disorders
    Decreased appetite 1/9 (11.1%)
    Dyslipidaemia 1/9 (11.1%)
    Hypokalaemia 2/9 (22.2%)
    Hypomagnesaemia 1/9 (11.1%)
    Increased appetite 1/9 (11.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/9 (11.1%)
    Nervous system disorders
    Dizziness 1/9 (11.1%)
    Psychiatric disorders
    Anxiety 1/9 (11.1%)
    Insomnia 1/9 (11.1%)
    Mood altered 1/9 (11.1%)
    Nightmare 1/9 (11.1%)
    Reactive psychosis 1/9 (11.1%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/9 (11.1%)
    Dermal cyst 1/9 (11.1%)
    Dermatitis acneiform 2/9 (22.2%)
    Pruritus 2/9 (22.2%)
    Rash 2/9 (22.2%)
    Vascular disorders
    Peripheral coldness 1/9 (11.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis PharmaCeuticals
    Phone 862-778-8300
    Email novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02468193
    Other Study ID Numbers:
    • CLCI699C1201
    First Posted:
    Jun 10, 2015
    Last Update Posted:
    May 6, 2020
    Last Verified:
    Apr 1, 2020