A Study of ATR-101 for the Treatment of Endogenous Cushing's Syndrome

Study Overview
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Brief Summary
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This is a Phase 2 multicenter, randomized, double-blind, placebo controlled study of ATR-101 to evaluate the efficacy and safety of orally-administered ATR-101 in adults with endogenous Cushing's syndrome. Following wash-out (if needed), all eligible subjects will enter an open-label intra-subject dose-escalation period of 8 weeks' duration, followed either by a double-blind randomized withdrawal period of 4 weeks' duration (if the subject meets randomization criteria) or by an additional open label dosing period of 4 weeks' duration (if the subject does not meet randomization criteria).It is anticipated that the overall duration of the study per subject will range from approximately 16-22 weeks.

Official Title
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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ATR-101 for the Treatment of Cushing's Syndrome

Conditions
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Cushing Syndrome

Intervention / Treatment
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* Drug: ATR-101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of endogenous Cushing's syndrome Baseline UFC 1.3 to 10 × upper limit of normal (ULN) If previous pituitary surgery, participants must be at least 3 months since surgery at the time of screening BMI between 18 and 60 kg/m2, inclusive Exclusion Criteria: Pseudo-Cushing's syndrome, cyclic Cushing's syndrome or current iatrogenic Cushing's syndrome Candidates for surgical treatment of Cushing's syndrome, unless surgery is not anticipated to occur during the study Normal late night salivary cortisol or 24-hr urine free cortisol Radiotherapy of the pituitary within 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATR-101<br>During the 4-week randomized withdrawal period, eligible subjects will receive ATR-101 at the same dose level being used at the completion of the open-label dose-escalation period. | Drug: ATR-101<br>* During the 4-week randomized withdrawal period, subjects will be dosed for 4 weeks at the same dose level being used at the completion of the open-label dose-escalation period.<br>* Other names: nevanimibe HCl;|
| Placebo Comparator: Placebo<br>During the 4-week randomized withdrawal period, eligible subjects will receive a placebo that matches the same ATR-101 dose level being used at the completion of the open-label dose-escalation period. | Drug: Placebo<br>* During the 4-week randomized withdrawal period, subjects will be dosed for 4 weeks with placebo that matches the same ATR-101 dose level being used at the completion of the open-label dose-escalation period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects With Either a Normal 24-hr Urinary Free Cortisol (UFC) or a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value | The number of subjects meeting the criterion was divided by the total number of subjects. | Through Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion of Subjects With a Normal 24-hr UFC | The number of subjects meeting the criterion was divided by the total number of subjects. | Through Day 85 | 
| The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value | The number of subjects meeting the criterion was divided by the total number of subjects. | Through Day 85 | 
| The Proportion of Subjects With a Normal 24-hr UFC | The number of subjects meeting the criterion was divided by the total number of subjects. | Through Day 57 and Day 85 | 
| The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value | The number of subjects meeting the criterion was divided by the total number of subjects. | Through Day 57 and Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endogenous Cushing's Syndrome, ATR-101, CS