Trial Outcomes & Findings for Treatment of Cushing's Disease With R-roscovitine (NCT NCT02160730)

Results Overview

To evaluate the efficacy of R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks on normalizing 24 hour urinary free cortisol (24 h UFC) levels in CD patients. "Normalizing" is defined as having urine free cortisol levels within the normal range for that lab value.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

Baseline, 4 weeks

Results posted on

2021-11-04

Participant Flow

Patients on medical treatment for CD must complete washout periods before screening assessments are performed: Inhibitors of steroidogenesis (metyrapone, ketoconazole): 2 weeks; somatostatin receptor ligand (SRL; pasireotide): short-acting, 2 weeks; long active, 4 weeks; progesterone receptor antagonist (mifepristone): 2 weeks; dopamine agonists (cabergoline): 4 weeks; CYP3A4 strong inducers or inhibitors: varies between drugs, minimum 5-6 x the drug half-life.

Participant milestones

Participant milestones
Measure	R-roscovitine • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks.
Overall Study STARTED	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks.
Age, Continuous	46.5 years STANDARD_DEVIATION 12.9 • n=4 Participants
Sex: Female, Male Female	4 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=4 Participants
Region of Enrollment United States	4 participants n=4 Participants
Baseline Mean Urine Free Cortisol (mcg/24hr)	233.3 mcg/24hr STANDARD_DEVIATION 108.7 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, 4 weeks

To evaluate the efficacy of R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks on normalizing 24 hour urinary free cortisol (24 h UFC) levels in CD patients. "Normalizing" is defined as having urine free cortisol levels within the normal range for that lab value.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Number of Participants With a Normalized 24 Hour Urinary Free Cortisol After 4 Weeks	0 Participants

SECONDARY outcome

Timeframe: Baseline, 4 Weeks

HbA1c levels are measured at baseline and at study end, these are averaged across all subjects.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Change in Mean HbA1c Levels Between Baseline and 4 Weeks Baseline	6.9 Percentage Standard Deviation 1.02
Change in Mean HbA1c Levels Between Baseline and 4 Weeks Study End-4 weeks	7 Percentage Standard Deviation 1.18

SECONDARY outcome

Timeframe: Baseline, 4 weeks

The number of participants that experience an adverse event between baseline and study end likely related to study drug as a measure of safety and tolerability.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Number of Participants With Adverse Events	2 Participants

SECONDARY outcome

Timeframe: Baseline, 4 weeks

A visible change in tumor size as determined by the investigator after reviewing MRI reports between baseline and 4 weeks of treatment.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Number of Participants That Have a Visible Change in Tumor Size	0 Participants

SECONDARY outcome

Timeframe: Baseline, Week 4

The number of participants that achieved a urinary free cortisol level above the upper limit of the normal range but reduced by ≥50% from baseline at week 4.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Number of Participants That Experience Changes in Clinical Signs of Hypercortisolemia	2 Participants

SECONDARY outcome

Timeframe: Baseline, 4 Weeks

Mean change between baseline and week 4 of fasting blood glucose levels.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Fasting Glucose at Baseline and 4 Weeks Baseline	121.4 g/dL Standard Deviation 30.5
Fasting Glucose at Baseline and 4 Weeks 4 weeks	104.3 g/dL Standard Deviation 25

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Mean change in Plasma ACTH between baseline and 4 weeks.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Plasma ACTH at Baseline and 4 Weeks Baseline	79.3 pg/mL Standard Deviation 30.3
Plasma ACTH at Baseline and 4 Weeks 4 weeks	79.9 pg/mL Standard Deviation 32.1

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Change in typical Cushing's syndrome clinical signs and symptoms defined by mean weight at baseline and 4 weeks.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Change in Clinical Symptoms Baseline	217 lbs Standard Deviation 78.6
Change in Clinical Symptoms 4 Weeks	217.4 lbs Standard Deviation 80.6

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Mean serum cortisol values at baseline and 4 weeks

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Changes in Serum Cortisol Between Baseline and 4 Weeks Baseline	25.6 mg/dL Standard Deviation 5.5
Changes in Serum Cortisol Between Baseline and 4 Weeks 4 Weeks	27.1 mg/dL Standard Deviation 8.7

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Mean change in systolic blood pressure between baseline and 4 weeks.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Change in Systolic Blood Pressure Baseline	150.3 mmHg Standard Deviation 18.8
Change in Systolic Blood Pressure 4 weeks	128.3 mmHg Standard Deviation 6.0

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Mean diastolic blood pressure between baseline and 4 weeks.

Outcome measures

Outcome measures
Measure	R-roscovitine n=4 Participants • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks. R-roscovitine: See Arm Description
Change in Diastolic Blood Pressure Baseline	76.5 mmHg Standard Deviation 12.2
Change in Diastolic Blood Pressure 4 Weeks	71 mmHg Standard Deviation 10

Adverse Events

R-roscovitine

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	R-roscovitine n=4 participants at risk • R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks.
Hepatobiliary disorders Elevated Liver Enzymes	25.0% 1/4 • Number of events 1 • From screening through 1 week after last dose, up to 5 weeks.
Renal and urinary disorders Elevated Creatinine Levels	25.0% 1/4 • Number of events 1 • From screening through 1 week after last dose, up to 5 weeks.

Additional Information

Dr. Ning-Ai Liu

Cedars-Sinai Medical Center

Phone: 310-423-7382

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place