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Trial · Interventional

CompletedPhase 2Results postedRegistry data

Safety and Efficacy of LCI699 in Cushing's Disease Patients

NCTNCT01331239 (opens ClinicalTrials.gov in a new tab)Other idCLCI699C2201Other id2010-022403-22
Open at ClinicalTrials.govAsk about this trial

This trial does not test a peptide that PepBank tracks.

  • Measures ACTH (corticotropin), does not give it. It appears in the eligibility rules.

Overview

Status
Completed
Phase
Phase 2
Enrollment
31 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Not randomized · Open label (no masking)
Countries
4 countries

United States, France, Italy, Japan

Start
23 Mar 2011
Primary completion
22 Oct 2019
Completion
22 Oct 2019
First posted
8 Apr 2011 (estimated)
Last update posted
22 Jan 2021
Conditions
Cushings Disease · Cushing Disease

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20122014201620182020
  1. Ph 2

    Safety and Efficacy of LCI699 in Cushing's Disease Patients

    NCT01331239

    23 Mar 2011 to 22 Oct 2019

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • LCI699Drug

Arms3

  • Experimental

    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 I of this study. 4 patients in this cohort moved to Part II of the study

  • Experimental

    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 II Core Expansion of this study. These patients were all newly enrolled into the phase II part of the study

  • Experimental

    Part II 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 II Core Follow-up of this study. These patients were patients who transferred from Part I Core phase of the study

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percentage of Responders to LCI699 Based on the Change in Mean Urinary Free Cortisol (UFC) From Baseline to Week 10

    Time frame · 10 weeks

    Registry description

    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.

Secondary outcomes(20)

  1. Actual Change From Baseline (BL) in Steroid Hormones of Hypothalamic-Pituitary-Adrenal (HPA)-Axis: 11- Deoxycorticosterone (Overall)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in Deoxycorticosterone over time.

  2. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: 11-Deoxycortisol (Overall)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in Deoxycortisol over time.

  3. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Aldosterone, Thyroxine, Free (T4)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in aldosterone \& thyroxine, free over time.

  4. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Female)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in Estradiol in females over time.

  5. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Estradiol (Male)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in Estradiol in males over time.

  6. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (FSH) (Female)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in FSH in females over time.

  7. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Follicle Stimulation Hormone (Male)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in FSH in males over time.

  8. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Renin, Insulin, Thyrotropin

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in Renin, Insulin \& Thyrotropin over time.

  9. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Insulin-like Growth Factor-1

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in Insulin-like Growth Factor-1 over time.

  10. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Luteinising Hormone (LH) (Female)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in LH in females over time.

  11. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: LH (Male)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in LH in males over time.

  12. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Female)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in Testosterone in females over time.

  13. Actual Change From Baseline (BL) in Steroid Hormones of HPA-axis: Testosterone (Male)

    Time frame · baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

    Registry description

    Change in Testosterone in males over time.

  14. Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Fasting Glucose

    Time frame · Baseline, Week 22, Week 70, Last observed value, up to Month 88

    Registry description

    Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.

  15. Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Hemoglobin A1C (HbA1C) (Glycosylated Hemoglobin)

    Time frame · Baseline, Week 22, Week 70, Last observed value, up to Month 88

    Registry description

    Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.

  16. Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides

    Time frame · Baseline, Week 22, Week 70, Last observed value, up to Month 88

    Registry description

    Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.

  17. Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Sitting Diastolic Blood Pressure (DBP), Sitting Systolic Blood Pressure (SBP)

    Time frame · Baseline, Week 22, Week 70, Last observed value, up to Month 88

    Registry description

    Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.

  18. Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Weight

    Time frame · Baseline, Week 22, Week 70, Last observed value, up to Month 88

    Registry description

    Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.

  19. Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Body Mass Index (BMI)

    Time frame · Baseline, Week 22, Week 70, Last observed value, up to Month 88

    Registry description

    Improving metabolic abnormalities was assessed by descriptive statistics on the change from baseline.

  20. Actual Change From BL in Cardiovascular and Other Metabolic Parameters: Quantitative Insulin Sensitivity Check Index (QUICKI)

    Time frame · Baseline, Week 22, Week 70, Last observed value, up to Month 88

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· 10 weeks

Percentage of Responders to LCI699 Based on the Change in Mean Urinary Free Cortisol (UFC) From Baseline to Week 10

GroupValue (Percentage of participants)
Part l: Core Cohort100.0
Secondary and other outcome results(7)
Secondary outcomeMean· baseline, Week 22, Week 70, Last observed value (LOV), up to Month 88

Actual Change From Baseline (BL) in Steroid Hormones of Hypothalamic-Pituitary-Adrenal (HPA)-Axis: 11- Deoxycorticosterone (Overall)

GroupValue (pmol/L)Spread
Part II Core: Expansion Cohort292.8371.54
Part ll Core: Follow-up Cohort188.0105.21
Secondary outcomeMean· 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)

GroupValue (nmol/L)Spread
Part II Core: Expansion Cohort4.214.648
Part ll Core: Follow-up Cohort5.486.549
Secondary outcomeMean· 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)

GroupValue (pmol/L)Spread
Part II Core: Expansion Cohort165.5255.07
Part ll Core: Follow-up Cohort127.0177.04
Secondary outcomeMean· 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)

GroupValue (pmol/L)Spread
Part II Core: Expansion Cohort209.60282.423
Part ll Core: Follow-up Cohort307.23263.028
Secondary outcomeMean· 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)

GroupValue (pmol/L)Spread
Part II Core: Expansion Cohort55.0025.755
Part ll Core: Follow-up Cohort77.10NA
Secondary outcomeMean· 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)

GroupValue (U/L)Spread
Part II Core: Expansion Cohort9.0913.277
Part ll Core: Follow-up Cohort2.430.929
Secondary outcomeMean· 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)

GroupValue (U/L)Spread
Part II Core: Expansion Cohort5.883.241
Part ll Core: Follow-up Cohort5.80NA

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Part l: Core CohortParticipants 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 study0 / 121 / 1212 / 12
Part ll Core: Expansion CohortParticipants 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 study0 / 155 / 1515 / 15
Part ll Core: Follow-up CohortParticipants 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 study0 / 41 / 44 / 4

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedFleseriu 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. PMID 41052284
  • DerivedBertagna 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. PMID 24423285

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 75 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Patients with a confirmed diagnosis of Cushing's Disease (persistent or recurrent) as evidenced by increased 24-hour urine free cortisol (UFC), normal or increased morning plasma Adrenocorticotropic Hormone (ACTH), and pituitary origin of excess ACTH. * Patients with de novo Cushing's disease can be included only if they are not considered candidate for surgery Exclusion Criteria: * Patients treated with mitotane 6 months prior to Visit 1 * Patients with compression of the optic chiasm * Patients with a known inherited syndrome as the cause for hormone over secretion * Patients with Cushing's syndrome due to ectopic ACTH secretion or adrenal Cushing's syndrome * Patients with pseudo-Cushing's syndrome * Patients who are not biochemically euthyroid * Diabetic patients with poorly controlled diabetes (HbA1c \>9%) * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after completion of dosing. * Patients who have received pituitary irradiation within five years prior to Visit 1. * Patients with risk factors for QTc prolongation or Torsade de Pointes.

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