A Phase 2 interventional study of R-roscovitine in Cushings Disease, sponsored by Shlomo Melmed, MD. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-11-04.
Sponsored by Shlomo Melmed, MD · Phase 2, Interventional, and Treatment
The investigators hypothesize that R-roscovitine will suppress pituitary corticotroph tumor ACTH production and normalize urinary free cortisol levels in patients with Cushing disease. To date, R-roscovitine has been evaluated in several Phase I and II studies and has shown early signs of anti-cancer activity in approximately 240 patients.
To date, R-roscovitine (seliciclib) has been evaluated in several Phase I and II studies and has shown early signs of anti-cancer activity in approximately 240 patients. Studies included a Phase I study in which single agent seliciclib was administered to patients with advanced non-small cell lung cancer (NSCLC) and two Phase IIa studies in which seliciclib was administered in combination with gemcitabine and cisplatin as first-line treatment and with docetaxel as second-line treatment in NSCLC. Seliciclib was also evaluated in a Phase I study in patients with nasopharyngeal cancer (NPC) with evidence of tumor shrinkage and concomitant reduction in copy counts of the EBV virus that is causally associated with the pathogenesis of NPC. Results from APPRAISE, a randomized discontinuation, double-blinded, placebo-controlled, Phase IIb study of oral seliciclib capsules as a monotherapy in heavily pretreated patients with NSCLC, demonstrated no difference between the seliciclib and placebo arms in progression free survival but a substantial increase in overall survival was observed (388 versus 218 days respectively (Cyclacel Pharmaceuticals press release Dec 21, 2010). Here, the investigators propose an exploratory, proof of concept clinical trial to determine if seliciclib can safely normalize urinary free cortisol levels by reducing pituitary corticotroph tumor ACTH production in patients with Cushing disease.
16 studies on the registry are indexed under Adrenocortical Hyperfunction; 1 is open to participants now.
Browse Adrenocortical Hyperfunction studies →This is the only study on the registry with Shlomo Melmed, MD as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients with confirmed pituitary origin of excess adrenocorticotropic hormone (ACTH) production:
Exclusion criteria:
Patients who have impairment in cardiovascular function or are at risk thereof, as evidenced by
Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results, such as
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
• R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks.
Drug: R-roscovitine
See Arm Description
Also known as: Seliciclib, CYC202
Number of Participants With a Normalized 24 Hour Urinary Free Cortisol After 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.
Time frame: Baseline, 4 weeks
Change in Mean HbA1c Levels Between Baseline and 4 Weeks
HbA1c levels are measured at baseline and at study end, these are averaged across all subjects.
Time frame: Baseline, 4 Weeks
Number of Participants With Adverse Events
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.
Time frame: Baseline, 4 weeks
Number of Participants That Have a Visible Change in Tumor Size
A visible change in tumor size as determined by the investigator after reviewing MRI reports between baseline and 4 weeks of treatment.
Time frame: Baseline, 4 weeks
Number of Participants That Experience Changes in Clinical Signs of Hypercortisolemia
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.
Time frame: Baseline, Week 4
Fasting Glucose at Baseline and 4 Weeks
Mean change between baseline and week 4 of fasting blood glucose levels.
Time frame: Baseline, 4 Weeks
Plasma ACTH at Baseline and 4 Weeks
Mean change in Plasma ACTH between baseline and 4 weeks.
Time frame: Baseline, 4 weeks
Change in Clinical Symptoms
Change in typical Cushing's syndrome clinical signs and symptoms defined by mean weight at baseline and 4 weeks.
Time frame: Baseline, 4 weeks
Changes in Serum Cortisol Between Baseline and 4 Weeks
Mean serum cortisol values at baseline and 4 weeks
Time frame: Baseline, 4 weeks
Change in Systolic Blood Pressure
Mean change in systolic blood pressure between baseline and 4 weeks.
Time frame: Baseline, 4 weeks
Change in Diastolic Blood Pressure
Mean diastolic blood pressure between baseline and 4 weeks.
Time frame: Baseline, 4 weeks
| Milestone | R-roscovitine |
|---|---|
| Started | 4 |
| Completed | 4 |
| Not completed | 0 |
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.
| Participants | R-roscovitine |
|---|---|
| Number of Participants With a Normalized 24 Hour Urinary Free Cortisol After 4 Weeks | 0 |
HbA1c levels are measured at baseline and at study end, these are averaged across all subjects.
| Percentage | R-roscovitine |
|---|---|
| Baseline | 6.9 ± 1.02 |
| Study End-4 weeks | 7 ± 1.18 |
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.
| Participants | R-roscovitine |
|---|---|
| Number of Participants With Adverse Events | 2 |
A visible change in tumor size as determined by the investigator after reviewing MRI reports between baseline and 4 weeks of treatment.
| Participants | R-roscovitine |
|---|---|
| Number of Participants That Have a Visible Change in Tumor Size | 0 |
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.
| Participants | R-roscovitine |
|---|---|
| Number of Participants That Experience Changes in Clinical Signs of Hypercortisolemia | 2 |
Mean change between baseline and week 4 of fasting blood glucose levels.
| g/dL | R-roscovitine |
|---|---|
| Baseline | 121.4 ± 30.5 |
| 4 weeks | 104.3 ± 25 |
Mean change in Plasma ACTH between baseline and 4 weeks.
| pg/mL | R-roscovitine |
|---|---|
| Baseline | 79.3 ± 30.3 |
| 4 weeks | 79.9 ± 32.1 |
Change in typical Cushing's syndrome clinical signs and symptoms defined by mean weight at baseline and 4 weeks.
| lbs | R-roscovitine |
|---|---|
| Baseline | 217 ± 78.6 |
| 4 Weeks | 217.4 ± 80.6 |
Mean serum cortisol values at baseline and 4 weeks
| mg/dL | R-roscovitine |
|---|---|
| Baseline | 25.6 ± 5.5 |
| 4 Weeks | 27.1 ± 8.7 |
Mean change in systolic blood pressure between baseline and 4 weeks.
| mmHg | R-roscovitine |
|---|---|
| Baseline | 150.3 ± 18.8 |
| 4 weeks | 128.3 ± 6.0 |
Mean diastolic blood pressure between baseline and 4 weeks.
| mmHg | R-roscovitine |
|---|---|
| Baseline | 76.5 ± 12.2 |
| 4 Weeks | 71 ± 10 |
Collected over From screening through 1 week after last dose, up to 5 weeks.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| R-roscovitine | 0/4 (0%) | 0/4 (0%) | 2/4 (50%) |
| Event | R-roscovitine |
|---|---|
| Elevated Liver EnzymesHepatobiliary disorders | 1/4 |
| Elevated Creatinine LevelsRenal and urinary disorders | 1/4 |
| Age, Continuous(years) | R-roscovitine |
|---|---|
| Mean | 46.5 ± 12.9 |
| Sex: Female, Male(Participants) | R-roscovitine |
|---|---|
| Female | 4 |
| Male | 0 |
| Race and Ethnicity Not Collected(Participants) | R-roscovitine |
|---|
| Region of Enrollment(participants) | R-roscovitine |
|---|---|
| United States | 4 |
| Baseline Mean Urine Free Cortisol (mcg/24hr)(mcg/24hr) | R-roscovitine |
|---|---|
| Mean | 233.3 ± 108.7 |
PDFs hosted by the registry, ClinicalTrials.gov.
This study is terminated, as verified in Nov 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Roscovitine
Adrenocortical Hyperfunction →