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Slow enrollment
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ATR-101 | Experimental | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATR-101 | Drug | 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. |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James Findling, MD | Medical College of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| The Cleveland Clinic Foundation |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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 | Posted | Count of Participants | Participants | Through Day 85 |
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Adverse events were collected from the time of informed consent until 30 days after the last dose of study drug
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
Early termination leading to small numbers of subjects analyzed
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Information | Millendo Therapeutics | +1 734 845-9000 | millendo@millendo.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 14, 2018 | Jan 25, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 18, 2019 | Jan 25, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003480 | Cushing Syndrome |
| ID | Term |
|---|---|
| D000308 | Adrenocortical Hyperfunction |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C079534 | N-(2,6-bis(1-methylethyl)phenyl)-N'-((1-(4-(dimethylamino)phenyl)cyclopentyl)methyl)urea hydrochloride |
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| Placebo | Drug | 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. |
|
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 |
| Cleveland |
| Ohio |
| 44195 |
| United States |
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53051 | United States |
| The James Cook University Hospital | Middlesbrough | TS4 3 BW | United Kingdom |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Weight | Mean | Standard Deviation | kg |
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| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
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| 24-hr Urinary Free Cortisol | 24-hr urine samples were collected and assayed for free cortisol by liquid chromatography-tandem mass spectrometry | Mean | Standard Deviation | ug/day |
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| Counts |
|---|
| 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. | 4 patients were analyzed. None ("0") of them showed a normal 24-hr urinary free cortisol (UFC) | Posted | Count of Participants | Participants | Through Day 85 |
|
|
|
| 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. | 4 patients were analyzed. None ("0") of them showed a reduction in 24-hr UFC of ≥ 50% relative to their baseline value | Posted | Count of Participants | Participants | Through Day 85 |
|
|
|
| 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. | 4 patients were analyzed at Day 57 and Day 85. None ("0") of them showed a normal 24-hr urinary free cortisol (UFC). | Posted | Count of Participants | Participants | Through Day 57 and Day 85 |
|
|
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| 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. | 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 | Posted | Count of Participants | Participants | Through Day 57 and Day 85 |
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| 0 |
| 4 |
| 0 |
| 4 |
| 3 |
| 4 |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Ear discomfort | Ear and labyrinth disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Abdominal distention | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Peripheral swelling | General disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | MedDRA (18.0) | Non-systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDRA (18.0) | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (18.0) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (18.0) | Non-systematic Assessment |
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