Efficacy and Safety Evaluation of Osilodrostat in Cushing's Disease (LINC-4)
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|ClinicalTrials.gov Identifier: NCT02697734|
Recruitment Status : Recruiting
First Posted : March 3, 2016
Last Update Posted : September 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Cushing's Disease||Drug: osilodrostat Drug: osilodrostat Placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||69 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||A Phase III, Multi-center, Randomized, Double-blind, 48 Week Study With an Initial 12 Week Placebo-controlled Period to Evaluate the Safety and Efficacy of Osilodrostat in Patients With Cushing's Disease|
|Actual Study Start Date :||October 3, 2016|
|Estimated Primary Completion Date :||October 25, 2019|
|Estimated Study Completion Date :||October 25, 2019|
Experimental: osilodrostat Group
Participants are randomized in a 2:1 ratio to treatment with study drug (osilodrostat or placebo, respectively),
In the form of filmcoated tablets for oral administration, in the following dose strengths: 1 mg, 5 mg, 10 mg, and 20 mg. Each strength has a unique size and color. The osilodrostat 1 mg, 5 mg, 10 mg and 20 mg film coated tablets are approximately 6 mm, 7 mm, 9 mm, and 11 mm respectively in diameter and pale yellow, yellow, pale orange brown and light brown respectively in color.
Other Name: LCI699
Placebo Comparator: osilodrostat Placebo Group
Participants are randomized in a 2:1 ratio to treatment with study drug (osilodrostat or placebo, respectively)
Drug: osilodrostat Placebo
Matching Placebo in the form of filmcoated tablets for oral administration, in the following dose strengths: 1 mg, 5 mg, 10 mg, and 20 mg. Each strength has a unique size and color.
- Percentage of randomized participants with a complete response [ Time Frame: at Week 12 ]To demonstrate the superiority of osilodrostat compared to placebo in achieving a complete response mean urine free cortisol ≤ upper limit of normal (mUFC ≤ ULN) at Week 12.
- Percentage of participants with mUFC ≤ ULN [ Time Frame: At Week 36 ]To assess the complete response rate in both arms combined at Week 36 in patients receiving osilodrostat treatment.
- Percentage of patients with complete response mUFC ≤ ULN and partial response with mUFC decrease ≥ 50% from baseline and > ULN) [ Time Frame: At Week 12, Week 36, and Week 48 ]The assess the percentage of patients with a complete response (mUFC ≤ ULN) or a partial response (mUFC decrease ≥ 50% from baseline and >ULN) at Week 12, Week 36, and Week 48.
- Percentage change in mUFC [ Time Frame: Baseline, weeks 2,5,8,12,14,17,20,23,26,29,32,36,40,48,60,72,84,96 ]To assess the complete response by treatment arm from baseline to week 2,5,8,12,14,17,20,23,26,29,32,36,40,48,60,72,84,96 by treatment arm for all participants.
- Time-to-first control of mUFC [ Time Frame: At randomization, day 1,15,36,57,85. ]To assess time-to-first control of mUFC, (in days) from randomization to the first mUFC collection that was ≤ ULN before completion/discontinuation of placebo-controlled period.
- Time-to-escape from collection of normal mUFC (≤ ULN) to the first mUFC > 1.3 x ULN [ Time Frame: At week 48 ]To assess time-to-escape from the first collection of normal mUFC (≤ ULN) to the first mUFC > 1.3 x ULN on two consecutive visits on the highest tolerated dose of osilodrostat and not related to a dose interruption or dose reduction due to safety reasons. Escape will not be assessed for participants during the first 26 weeks.
- Percent change in fasting plasma glucose, HbA1c, fasting lipid profile, blood pressure, weight and waist circumference) [ Time Frame: Baseline, weeks 12, 36, and 48 ]To assess percent change from baseline in fasting plasma glucose, HbA1c, fasting lipid profile, blood pressure, weight and waist circumference at Week12, Week 36, and Week 48 by treatment arm and for the overall participant population.
- Change from baseline in bone mineral density (BMD) by Dual-energy X-ray absorptiometry (DXA) scan at the lumbar spine and total hip [ Time Frame: Baseline, week 48 ]The change from baseline in bone mineral density, and BMD T- score, at the lumbar spine (L1-L4) and total hip at Week 48 by treatment arm and for overall participant population.
- Change from baseline in Health Related Quality of Life, using Cushing Disease-specific Quality of Life, Beck Depression Inventory II (BDI-I), EQ-5D-5L [ Time Frame: Baseline to Week 12 and 48, Week 12 to Week 36, Week 36 to Week 48. ]Change in standardized score of CushingQoL, Beck Depression Inventory-II, and EQ-5D-5L, from baseline to Week 12 and Week 48, from Week 12 to Week 36, and from Week 36 to Week 48, or the last measurement prior to early discontinuation, whichever occurs earlier in treatment arm and overall participant population.
- Percent of patients with a complete response (mUFC ≤ ULN) or a partial response (mUFC decrease ≥ 50% from baseline and >ULN) at week 12, 36 and 48 [ Time Frame: Baseline, week 12, 36 and 48 ]To assess the overall response rate defined as percentage of complete responders (mUFC ≤ ULN) plus partial responders (≥ 50% reduction in mUFC from baseline and >ULN) at week 12, 36, 48 by treatment arms for all patients.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02697734
|Contact: Novartis Pharmaceuticalsfirstname.lastname@example.org|
|Contact: Novartis Pharmaceuticalsemail@example.com|
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|