Cushing Syndrome
Conditions
Keywords
Endogenous Cushing's Syndrome, ATR-101, CS
Brief summary
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.
Interventions
DRUGATR-101
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.
DRUGPlacebo
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.
Sponsors
Millendo Therapeutics US, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Through Day 85 | The number of subjects meeting the criterion was divided by the total number of subjects. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects With a Normal 24-hr UFC | Through Day 85 | The number of subjects meeting the criterion was divided by the total number of subjects. |
| The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value | Through Day 85 | The number of subjects meeting the criterion was divided by the total number of subjects. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ATR-101 (Nevanimibe HCl) Subjects received nevanimibe orally 250 mg BID for 2 weeks, then 500 mg BID for 2 weeks, then 1000 mg BID for 2-4 weeks. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not meet randomization criteria | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | ATR-101 (Nevanimibe HCl) |
|---|---|
| 24-hr Urinary Free Cortisol | 198.84 ug/day STANDARD_DEVIATION 147.071 |
| Age, Continuous | 44.3 years STANDARD_DEVIATION 9.18 |
| Body Mass Index | 30.79 kg/m^2 STANDARD_DEVIATION 3.172 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United Kingdom | 1 participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 1 Participants |
| Weight | 86.42 kg STANDARD_DEVIATION 7.755 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 3 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
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.
Time frame: Through Day 85
Population: 4 patients were analyzed. None (0) of them showed a normal 24-hr urinary free cortisol (UFC) or a reduction in 24-hr UFC of ≥ 50% relative to their baseline value
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATR-101 (Nevanimibe HCl) | 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 | 0 Participants |
Secondary
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.
Time frame: Through Day 85
Population: 4 patients were analyzed. None (0) of them showed a normal 24-hr urinary free cortisol (UFC)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATR-101 (Nevanimibe HCl) | The Proportion of Subjects With a Normal 24-hr UFC | 0 Participants |
Secondary
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.
Time frame: Through Day 57 and Day 85
Population: 4 patients were analyzed at Day 57 and Day 85. None (0) of them showed a normal 24-hr urinary free cortisol (UFC).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ATR-101 (Nevanimibe HCl) | The Proportion of Subjects With a Normal 24-hr UFC | Day 57 | 0 Participants |
| ATR-101 (Nevanimibe HCl) | The Proportion of Subjects With a Normal 24-hr UFC | Day 85 | 0 Participants |
Secondary
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.
Time frame: Through Day 85
Population: 4 patients were analyzed. None (0) of them showed a reduction in 24-hr UFC of ≥ 50% relative to their baseline value
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ATR-101 (Nevanimibe HCl) | The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value | 0 Participants |
Secondary
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.
Time frame: Through Day 57 and Day 85
Population: 4 patients were analyzed at Day 57 and Day 85. None (0) of them showed a reduction in 24-hr UFC of ≥ 50% relative to their baseline value
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ATR-101 (Nevanimibe HCl) | The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value | Day 57 | 0 Participants |
| ATR-101 (Nevanimibe HCl) | The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value | Day 85 | 0 Participants |