Symptoms and General Pathology

All Conditions

Nervous System Diseases

Gland and Hormone Related Diseases

Heart and Blood Diseases

Neoplasms

Rare Diseases

Syndrome

Pituitary Diseases

Cushing Syndrome

Cardiac Complexes, Premature

ACTH-Secreting Pituitary Adenoma

Pituitary ACTH Hypersecretion

ACTH Syndrome, Ectopic

Adenoma

Adrenocortical Hyperfunction

Adrenal Gland Diseases

Endocrine System Diseases

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pituitary Neoplasms

Endocrine Gland Neoplasms

Cushing's Syndrome

ACTH-secreting Pituitary Adenoma

Hyperadrenalism

Reproductive Control Agents

All Drugs and Chemicals

Mifepristone

Contraceptive Agents

Contraceptives, Oral

Contraceptive Agents, Female

Contraceptives, Postcoital

Hormones

Hormone Antagonists

Contraceptive Agents, Hormonal

mifepristone at doses from 300mg/day up to 1200mg/day

Coleman Gross, M.D.

This is a compassionate use study. In addition to providing compassionate use access to mifepristone, objectives of the study will be to evaluate the safety and utility of mifepristone in the treatment of the signs and symptoms of endogenous Cushing's syndrome when given on a compassionate use basis. The study will only enroll subjects whose physicians have determined that medical treatment is needed to control the symptoms or signs of hypercortisolemia.

Compassionate Use of CORLUX® (Mifepristone) in the Treatment of Signs and Symptoms of Endogenous Cushing's Syndrome

Compassionate Use Protocol for the Administration of CORLUX® (Mifepristone) in the Treatment of the Signs and Symptoms of Endogenous Cushing's Syndrome

Safety was assessed at all visits and adverse events were recorded.

Corcept Therapeutics

All patients who received at least one dose of study drug are included.

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Subjects who received one dose of study drug were included in the safety analysis.

Medical Director

Due to the small number of patients enrolled (N=4), no formal assessments were planned. All patients who received study drug were included in the safety review.

Number of Participants With Adverse Events

Overall Study

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Lipodystrophy

Skin Diseases

Skin Diseases, Metabolic

Metabolic Diseases

Lipid Metabolism Disorders

Glucocorticoids

Surgical resection of ACTH-secreting tumor to achieve cure of hypercortisolism

Treatment of Cushing's

Gabrielle Page-Wilson, MD

This proposal will evaluate the glucocorticoid mediated changes in body fat distribution and metabolism that occur in patients with Cushing's disease. The objective is to identify the mechanisms that influence both the accumulation of lipodystrophic fat and also the changes in energy expenditure and metabolism that accompany them. The study is designed to determine if the high cortisol and AgRP levels in the blood of people living with Cushing's syndrome, either from taking steroid medications or from tumors, impact body fat and metabolism by turning off brown fat, which is a type of fat that increases one's metabolism.

Cushing's disease (CD) is a disorder of chronic glucocorticoid (GC) excess that gives rise to a constellation of metabolic comorbidities and to a distinct lipodystrophic body habitus characterized by central adiposity, extremity wasting, and the accumulation of supraclavicular (SC) and dorsocervical (DC) fat in the region where human brown and beige adipose tissue is known to be concentrated. In spite of the recognized thermogenic capacity of select cervical adipocytes, the potential impact of lipomatous alterations in this depot on energy balance and metabolism in CD is unknown. To our knowledge, the "buffalo hump" and the supraclavicular fat pads - which are a sensitive physical finding for CD, have never been phenotypically characterized and the mechanisms underlying the GC mediated development of fat in these depots and the associated metabolic complications have not been explored in humans. The proposed research will advance our understanding of Cushing's lipodystrophy and its metabolic complications. Furthermore, it may lead to the identification of novel mediators and targetable pathways to attenuate the adverse effects of hypercortisolism on body composition and metabolism in CD, as well as in the significant population of patients treated with chronic GCs for an array of other clinical conditions. These findings may have important implications not only for those with Cushing's disease, but for the millions of Americans who are treated with chronic glucocorticoids for an array of clinical conditions.

Subjects will undergo 4mm punch biopsies of the SC, DC, and subcutaneous abdominal fat pads under local anesthesia (lidocaine). Biopsies will be performed by an interventional radiologist or surgeon. Specimens will be prepared for histologic analysis and for immunohistochemical analysis for brown and white adipose tissue markers.

Novel Mediators of the Lipodystrophy and Metabolic Consequences of Cushing's Disease

Resting energy expenditure (REE) will be measured by whole room indirect calorimetry prior to and following cure of Cushing's Disease (CD).

Whole body MRI will be utilized to measure total body adipose tissue volume

New York Obesity and Nutrition Research Center

Columbia University

Assistant Professor of Medicine

Pheochromocytoma

Adrenal Gland Neoplasms

Hyperaldosteronism

Paraganglioma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Paragangliomas 1

Neuroendocrine Tumor

Neuroepithelioma

Posterior retroperitoneoscopic adrenalectomy

Lateral transperitoneal laparoscopic adrenalectomy

Posterior RA

Lateral transperitoneal LA

Marcin Barczyński, MD, PhD

Laparoscopic adrenalectomy has become the gold standard operation for non-malignant adrenal tumors replacing open adrenalectomy. The most popular lateral transperitoneal laparoscopic adrenalectomy (LTLA) approach has been recently challenged by an increasing popularity of the posterior retroperitoneoscopic adrenalectomy (PRA) approach which is believed by many surgeons as an easy to learn, reproducible and beneficial for patients. However, this belief is not evidence-based, so far. The aim of this study is to clarify if PRA is superior to the LTLA as minimally invasive approach to small and benign adrenal tumors.

Laparoscopic adrenalectomy has replaced open adrenalectomy as the standard operation for non-malignant adrenal tumours. Thanks to the popularization of the posterior technique described by Walz and co-workers, the posterior retroperitoneal adrenalectomy (PRA) is being performed in increasing numbers worldwide. Advocates for the laparoscopic and retroperitoneoscopic approaches cite the advantages of each technique, but there is no published evidence that supports the superiority of one over the other. Most of the published literature is retrospective, with inadequate or no controls and with potential biases.

The aim of this study is to test the hypothesis that PRA is superior to the lateral transperitoneal laparoscopic adrenalectomy (LTLA) as minimally invasive approach to small and benign adrenal tumors.

For a sample size calculation an assumption was made that a 20% reduction in duration of surgery represents clinically relevant difference. To detect this, it was calculated that 24 patients would be required in each treatment arm to give the study a power of 90 per cent. Anticipating a 25% loss to follow-up, 32 patients per arm were required in the study.

Randomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Laparoscopic Adrenalectomy

Randomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Transperitoneal Laparoscopic Adrenalectomy With a Five-year Follow-up

including: postoperative pain, length of hospital stay, time to oral intake, time to ambulation

including: pneumothorax/haemothorax, surgical emphysema, chest infection, visceral injury, peritonitis/abscess, wound infection, neuralgia, and surgical access site herniation

Jagiellonian University

Associate Professor of Surgery at the Third Chair of General Surgery

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Carcinoma

Hyperplasia

Adrenocortical Adenoma

Adrenocortical Carcinoma

Adrenal Hyperplasia, Congenital

Adrenogenital Syndrome

Adrenal Cortex Neoplasms

Adrenal Cortex Diseases

Adenocarcinoma

Paraneoplastic Syndromes

Adenoma of the Adrenal Gland

Congenital Adrenal Hyperplasia

21-hydroxylase Deficiency

ACTH-independent Macronodular Adrenal Hyperplasia

Vasoconstrictor Agents

Respiratory System Agents

Epinephrine

Racepinephrine

Epinephryl borate

Adrenocorticotropic Hormone

Patients in this arm took the study drug, osilodrostat.

Osirodrostat 1mg, 5mg \& 10mg in the form of film-coated tablets was used for oral administration.

Osilodrostat

Novartis Pharmaceuticals

The study aim was to investigate the efficacy and safety of Osilodrostat in patients with Cushing's syndrome due to causes other than Cushing's disease in Japan.

This was a Phase II, single arm, open-label, dose titration, multi-center study which consisted of two distinct Study Periods plus an optional extension period in non-CD patients with CS. The 3 Study Periods (two distinct Study Periods plus an optional extension period) were as follows:

Study Period I \[Week 0 (Day 1) to Week-12\]: Study Period I was the dose titration period to achieve a stable therapeutic dose and to assess the efficacy and safety of osilodrostat.

The dosing regimen of osilodrostat in this study was titrated according to the following escalation sequence: osilodrostat 2 mg bid, 5 mg bid, 10 mg bid, 20 mg bid, and 30 mg bid. Dose adjustments were based on the serum cortisol values measured by the local lab at each site. Osilodrostat titration was done weekly for the initial 4-weeks, up to a maximum dose of 10 mg bid.

The mean of three 24-hour UFC (mUFC) values were measured to evaluate the efficacy in this period.

Study Period II (After Week-12 to Week-48): Study Period II was the period to assess the sustainability of efficacy and long term safety.

During Study Period II, only patients who tolerated and agreed to continue osilodrostat treatment continued on the study. The patient was administered with the stable therapeutic dose which was achieved in the Study Period I.

Optional extension period (After Week-48): Patients who continued to receive clinical benefit, as assessed by the study Investigator and who wished to enter the extension period were reconsented at Week-48. Patients who entered the extension period continued to be treated with the study drug without interruption to be assessed for efficacy and safety. Patients who continued to benefit from study treatment as assessed by the study investigator and who completed Week-72 were offered to participate in a separate long-term safety follow-up study. The optional extension period ended after all patients had completed Week-72 or had discontinued early.

Post-treatment Follow-up: All patients had 30 days safety follow-up after the last dose of study treatment.

Study of Efficacy and Safety of Osilodrostat in Cushing's Syndrome

A Phase II, Open-label, Dose Titration, Multi-center Study to Assess the Safety/Tolerability and Efficacy of Osilodrostat in Patients With All Types of Endogenous Cushing's Syndrome Except Cushing's Disease

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com

Percent change from baseline in the mUFC at the individual patient level

Absolute change from baseline in the mUFC

Complete response rate = percentage of participants who had mUFC≤ ULN; Partial response rate = Percentage of participants who had mUFC\>ULN and at least 50% reduction from baseline in mUFC. Overall response rate = Percentage of participants who had mUFC ≤ ULN or at least 50% reduction from baseline.

Absolute change from baseline in morning serum cortisol at the individual patient level

Percentage change from baseline in morning serum cortisol at the individual patient level

Absolute change from baseline in several steroid hormones at individual levels: ACTH, Serum 11-deoxycorticosterone, Aldosterone, Estradiol

Percent change from baseline in several steroid hormones at individual levels: ACTH, Serum 11-deoxycorticosterone, Aldosterone, Estradiol

Absolute change from baseline in several steroid hormones at individual levels: Serum 11-deoxycortisol, Testosterone

Percent change from baseline in several steroid hormones at individual levels: Serum 11-deoxycortisol, Testosterone

Absolute change in cardiovascular-related metabolic parameter fasting glucose, associated with Cushing's syndrome (CS)

Percentasge change in cardiovascular-related metabolic parameter fasting glucose, associated with Cushing's syndrome (CS)

Absolute change in cardiovascular-related metabolic parameter HbA1c associated with Cushing's syndrome (CS)

Percentage change in cardiovascular-related metabolic parameter HbA1c associated with Cushing's syndrome (CS)

Absolute change in cardiovascular-related metabolic parameters: cholesterol, HDL cholesterol, LDL cholesterol \& triglycerides, associated with Cushing's syndrome (CS)

Percent change in cardiovascular-related metabolic parameters: cholesterol, HDL cholesterol, LDL cholesterol \& triglycerides, associated with Cushing's syndrome (CS)

Absolute change in cardiovascular-related metabolic parameter: BMI, associated with Cushing's syndrome (CS)

Percent change in cardiovascular-related metabolic parameter: BMI, associated with Cushing's syndrome (CS)

Absolute change in cardiovascular-related metabolic parameter: Waist circumference, associated with Cushing's syndrome (CS)

Percent change in cardiovascular-related metabolic parameter: Waist circumference, associated with Cushing's syndrome (CS)

Absolute change in cardiovascular-related metabolic parameter: sitting systolic BP \& sitting diastolic BP, associated with Cushing's syndrome (CS)

Percentage change in cardiovascular-related metabolic parameter: sitting systolic BP \& sitting diastolic BP, associated with Cushing's syndrome

The Cushing's Disease Health-Related Quality of Life Questionnaire (Cushing QoL) (version 1.0) was developed to evaluate quality of life in patients with Cushing's syndrome (Webb et al 2008). The Cushing QoL is comprised of 12 items that capture patient responses on seven concepts: daily activities, healing and pain, mood and self-confidence, social concerns, physical appearance, memory and concern about the future. Each questionnaire of the Cushing QOL has a scale of 1-5 where '1' corresponding to 'Always' or 'Very much' and '5' to 'Never' or 'Not at all'. The lower the score, the greater the impact on HRQoL. The score is the sum of all the item response and can range from 12 (worst) to 60 points (best).

The Beck Depression Inventory II (BDI-II) is a patient reported instrument that consists of 21 items designed to assess the intensity of depression in clinical \& normal patients in the preceding two weeks. Each item is a list of four statements arranged in increasing severity about a particular symptom of depression. Each of 21 items corresponds to a symptom of depression and the sum of total score will be calculated where each item has a four-point scale ranging from 0 to 3, leading to a total score from zero to 63.

Osilodrostat plasma concentration data at each time-point were summarized by incident dose. About a half of pre-dose concentration data were excluded from analysis due to deviation from the pre-defined acceptable time window.

AE description; Any sign or symptom that occurs during the study treatment plus the 30 days post treatment

Japanese

Race/Ethnicity, Customized

ACTH-Independent Macronodular Adrena;l Hyperplasia

Adrenal Adenoma

Ectopic Corticotropin Syndrome

Type of disease

Full Analysis Set (FAS): Comprised of all enrolled patients who received at least one dose of osilodrostat.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Compassionate Use of CORLUX® (Mifepristone) in the Treatment of Signs and Symptoms of Endogenous Cushing's Syndrome	NCT01371565	Cushing's Disea... Cushing's Syndr...	Mifepristone	18 Years -	Corcept Therapeutics
Novel Mediators of the Lipodystrophy and Metabolic Consequences of Cushing's Disease	NCT03817840	Cushing's Syndr...	Treatment of Cu...	18 Years - 70 Years	Columbia University
Randomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Laparoscopic Adrenalectomy	NCT01959711	Adrenal Tumor Pheochromocytom... Conn's Syndrome Cushing's Syndr...	Posterior RA Lateral transpe...	18 Years - 80 Years	Jagiellonian University
Study of Efficacy and Safety of Osilodrostat in Cushing's Syndrome	NCT02468193	Cushing's Syndr... Ectopic Cortico... Adrenal Adenoma Adrenal Carcino... AIMAH PPNAD	Osilodrostat	18 Years - 85 Years	Novartis
Preclinical Study Towards an Immunotherapy in Adrenocortical Carcinoma	NCT00457587	Adrenocortical ... Cushing's Syndr...		18 Years -	University of Wuerzburg
SPI-62 as a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome	NCT05307328	Cushing's Syndr... Cushing Disease... Cortisol Excess Cortisol; Hyper... Cortisol Overpr... Ectopic ACTH Se...	SPI-62 Placebo	18 Years -	Sparrow Pharmaceuticals
Novel Mediators of the Lipodystrophy and Metabolic Consequences of Cushing's Disease	NCT03817840	Cushing's Syndr...	Treatment of Cu...	18 Years - 70 Years	Columbia University
A Study to Assess SOM230 in Patients With Pituitary Cushing's Disease	NCT00088608	Cushing's Syndr...	SOM230 s.c.	18 Years - 80 Years	Novartis
Compassionate Use of CORLUX® (Mifepristone) in the Treatment of Signs and Symptoms of Endogenous Cushing's Syndrome	NCT01371565	Cushing's Disea... Cushing's Syndr...	Mifepristone	18 Years -	Corcept Therapeutics
Study of Adrenal Gland Tumors	NCT00005927	Adrenal Gland N...		3 Years - 70 Years	National Institutes of Health Clinical Center (CC)
Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the Carney Complex	NCT00001452	Cushing's Syndr... Pituitary Adeno... Carney Complex Primary Pigment... Peutz-Jeghers S...	oCRH	3 Years - 70 Years	National Institutes of Health Clinical Center (CC)

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