A Phase III Study of Osilodrostat to Treat Cushing’s Disease

CLCI699C2302: A Phase III, Multi-center, Randomized, Double-blind, 48 Week Study with an Initial 12 Week Placebo-controlled Period to Evaluate the Safety and Efficacy of Osilodrostat in Patients with Cushing’s Disease

Purpose

In people with a disorder known as Cushing’s disease, levels of the hormone cortisol are very high in the urine and blood. Lowering cortisol levels relieves the symptoms of Cushing’s disease. Osilodrostat is an investigational drug that inhibits an enzyme needed for cortisol to be made.

In this study, researchers are assessing the safety and effectiveness of osilodrostat in patients with Cushing¿s disease and observing its ability to reduce cortisol levels. In the first 12 weeks of the study, patients will receive osilodrostat or a placebo (inactive drug). After week 12 and continuing through week 48, all patients will receive osilodrostat. Patients will then have the option to continue taking osilodrostat for up to 100 weeks into the study, if they wish.

Osilodrostat is taken orally (by mouth).

Eligibility

To be eligible for this study, patients must meet several criteria, including but not limited to the following:

  • Patients must have Cushing¿s disease with elevated levels of cortisol in the urine.
  • An acceptable amount of time must have passed between the completion of prior therapies and entry into the study, to allow for a sufficient “washout” period.
  • This study is for patients ages 18 to 75.

For more information about this study and to inquire about eligibility, please contact Dr. Eliza Geer at 646-888-2627.

Protocol

17-351

Phase

III

Investigator

Co-Investigators

Diseases

Drug trial begins for Cushing’s syndrome therapy

Participant enrollment has concluded for a phase 3 trial investigating the safety and efficacy of levoketoconazole, a cortisol synthesis inhibitor, for the treatment of endogenous Cushing’s syndrome, according to a press release from Strongbridge Biopharma, the drug’s developer.

The single-arm, open-label SONICS study will include the 90 enrolled participants and may allow a small number of other patients to enroll also, according to the release.

After titration to a therapeutic dose of levoketoconazole (Recorlev), participants will maintain treatment for 6 months, the primary efficacy endpoint. Longer-term evaluation for safety will extend to 1 year. A planned 6-month double blind, placebo-controlled, randomized withdrawal extension, dubbed LOGICS, will include approximately half of the participants from SONICS.

“The need for a safe and effective, next-generation cortisol synthesis inhibitor, such as Recorlev, in the treatment of Cushing’s syndrome is substantial. Through achieving target enrollment in the SONICS study, we are one step closer to better understanding the clinical value of Recorlev and potentially bringing a new therapeutic treatment option to this community,” said Matthew Pauls, president and chief executive officer of Strongbridge Biopharma.

The company expects to announce results of SONICS in the second quarter of 2018 and of LOGICS in the third quarter, according to the release.

For more information:

Clinicaltrials.gov/ct2/show/NCT01838551

From https://www.healio.com/endocrinology/adrenal/news/online/%7Bdddb8b5b-e4c8-412f-b4b8-82acde8f21a2%7D/drug-trial-begins-for-cushings-syndrome-therapy

Phase 3 SONICS Study Evaluating RECORLEV™ (levoketoconazole) in Endogenous Cushing’s Syndrome

DUBLIN, Ireland and TREVOSE, Pa., June 27, 2017 (GLOBE NEWSWIRE) — Strongbridge Biopharma plc, (Nasdaq:SBBP), a global commercial-stage biopharmaceutical company focused on the development and commercialization of therapies for rare diseases with significant unmet needs, today announced that it has met its enrollment target of 90 patients in the Phase 3 SONICS study evaluating the safety and efficacy of RECORLEV(levoketoconazole), a next-generation cortisol synthesis inhibitor, for the treatment of endogenous Cushing’s syndrome. Based upon strong interest in the SONICS study at the end of screening, a small number of additional potential study participants remain in screening and will be allowed to enroll, if qualified.

“We would like to sincerely thank our investigators, their clinical teams, and, most importantly, all of the patients from many countries around the globe for their continued dedication and participation in the SONICS study,” said Fredric Cohen, M.D., chief medical officer of Strongbridge Biopharma. “We currently still have patients in screening for SONICS due to the high level of interest and demand in the study.  Although we have reached target enrollment, we are pleased to extend the study for a brief period to accommodate those in screening who qualify. This will enable us to report top-line results in the second quarter of 2018,” Dr. Cohen added.

“The need for a safe and effective, next-generation cortisol synthesis inhibitor, such as RECORLEV, in the treatment of Cushing’s syndrome is substantial. Through achieving target enrollment in the SONICS study, we are one step closer to better understanding the clinical value of RECORLEV and potentially bringing a new therapeutic treatment option to this community,” said Matthew Pauls, president and chief executive officer of Strongbridge Biopharma. “Because we strongly believe in the potential of RECORLEV to become a best-in-class therapy, and as previously announced, we have strengthened our Phase 3 development plan to include LOGICS, a nine-week, placebo-controlled study, which will complement the long-term SONICS study. We anticipate availability of top-line data from the LOGICS study in the third quarter of 2018,” Pauls added.

SONICS and LOGICS are multinational Phase 3 studies designed to evaluate the safety and efficacy of RECORLEV when used to treat endogenous Cushing’s syndrome. SONICS is a single-arm, open-label study conducted in three treatment phases. Patients titrate to a therapeutic dose in the first phase and are maintained at the therapeutic dose for six months in the second phase, the end of which marks the primary efficacy time point. A six-month extended evaluation is included for long-term safety evaluations. LOGICS uses a placebo-controlled, double-blind, randomized-withdrawal design. Approximately 35 patients with Cushing’s syndrome will be randomized in LOGICS, of which approximately one-half will have previously completed SONICS. Together, the SONICS and LOGICS studies will include the participation of approximately 100 clinical research sites in over 20 countries in North America, Europe and the Middle East.

For more information on the SONICS study, please visit ClinicalTrials.gov and reference identifier: NCT01838551.

About Endogenous Cushing’s Syndrome
Endogenous Cushing’s syndrome (CS) is a rare but serious and potentially lethal endocrine disease caused by chronic elevated cortisol exposure. Most people with CS have a variety of signs and symptoms – many of which, when they occur by themselves, are common and do not necessarily point to an underlying disease; this makes recognition of CS difficult. Common presenting symptoms include weight gain or obesity, fatigue, muscle weakness, headaches, mood or sleep disturbances, facial rounding or redness, excess body hair growth in women or baldness in men, thinned skin with stretch marks, easy bruising and other skin changes including acne, mood or sleep disturbances and irregular periods or loss of libido.  Patients are often found by their doctors to have new-onset or worsening of high blood pressure, abnormal levels of blood lipids, such as cholesterol, polycystic ovaries and abnormal blood glucose or diabetes. People with uncontrolled disease are seriously ill and have a 2- to 4-fold higher mortality rate than age- and gender-matched controls, mainly due to metabolic and cardiovascular complications. Treatment options for CS include surgery, radiation therapy, and medical treatment. Cushing’s syndrome most commonly affects adults ages 20-50 and is more prevalent in females, accounting for about 70 percent of all cases.

About Strongbridge Biopharma
Strongbridge Biopharma is a global commercial-stage biopharmaceutical company focused on the development and commercialization of therapies for rare diseases with significant unmet needs. Strongbridge’s first commercial product is KEVEYIS® (dichlorphenamide), the first and only FDA-approved treatment for hyperkalemic, hypokalemic, and related variants of Primary Periodic Paralysis. KEVEYIS has orphan drug exclusivity status in the U.S. through August 7, 2022. In addition to establishing this neuromuscular disease franchise, the Company has a clinical-stage pipeline of therapies for rare endocrine diseases. Strongbridge’s lead compounds include RECORLEV (levoketoconazole), a cortisol synthesis inhibitor currently being studied for the treatment of endogenous Cushing’s syndrome, and veldoreotide, a next-generation somatostatin analog being investigated for the treatment of acromegaly, with potential additional applications in Cushing’s syndrome and neuroendocrine tumors. Both RECORLEV and veldoreotide have received orphan designation from the U.S. Food and Drug Administration and the European Medicines Agency. For more information, visit www.strongbridgebio.com.

Forward-Looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties.  All statements, other than statements of historical facts, contained in this press release, are forward-looking statements. These statements relate to future events and involve known and unknown risks, including, without limitation, uncertainties regarding Strongbridge’s strategy, plans, anticipated investment, status and results of clinical trials and objectives of management for future operations. The words “anticipate,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “project,” “target,” “will,” “would,” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are based on current expectations, estimates, forecasts and projections and are not guarantees of future performance or development and involve known and unknown risks, uncertainties and other factors. The forward-looking statements contained in this press release are made as of the date of this press release, and Strongbridge Biopharma does not assume any obligation to update any forward-looking statements except as required by applicable law.

Contacts:

Corporate and Media Relations
Elixir Health Public Relations
Lindsay Rocco
+1 862-596-1304
lrocco@elixirhealthpr.com

Investor Relations
U.S.:
The Trout Group
Marcy Nanus
+1 646-378-2927
mnanus@troutgroup.com

Europe:
First House
Mitra Hagen Negård
+47 21 04 62 19
strongbridgebio@firsthouse.no

USA
900 Northbrook Drive
Suite 200
Trevose, PA 19053
Tel. +1 610-254-9200
Fax. +1 215-355-7389

From http://www.globenewswire.com/news-release/2017/06/27/1029452/0/en/Strongbridge-Biopharma-plc-Completes-Target-Enrollment-of-90-Patients-in-the-Phase-3-SONICS-Study-Evaluating-RECORLEV-levoketoconazole-in-Endogenous-Cushing-s-Syndrome.html

Study links genetic mutations, Cushing syndrome

Researchers have determined mutations in the gene CABLES1 may lead to Cushing syndrome, a rare disorder in which the body overproduces the stress hormone cortisol.

The National Institutes of Health study findings published in Endocrine-Related Cancer found four of the 181 children and adult patient examined had mutant forms of CABLES1 that do not respond to cortisol.

The determination proved significant because normal functioning CABLES1 protein, expressed by the CABLES1 gene, slows the division and growth of pituitary cells that produce the hormone adrenocorticotropin (ACTH).

Researchers at the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) joined scientists from other institutions in the United States, France and Canada, in the evaluation.

“The mutations we identified impair the tumor suppressor function in the pituitary gland,” Constantine A. Stratakis, the study’s senior author and director of the NICHD Division of Intramural Research, said. “This discovery could lead to the development of treatment strategies that simulate the function of the CABLES1 protein and prevent recurrence of pituitary tumors in people with Cushing syndrome.”

Cushing syndrome symptoms include obesity, muscle weakness, fatigue, high blood pressure, high blood sugar, depression and anxiety, officials said, adding excess cortisol found in the disorder can result from certain steroid medications or from tumors of the pituitary or adrenal glands.

Researchers maintain that more studies are needed to fully understand how CABLES1 suppresses tumor formation in the pituitary gland.

 

From https://lifesciencedaily.com/stories/21624-study-links-genetic-mutations-cushing-syndrome/

Cortisol: Chronic Stress Increases the Risk of Early Puberty

Scientists are trying to understand how childhood adversity affects puberty, but linking the two is difficult. Hair cortisol concentration (HCC) is a potentially useful biological marker of chronic stress. However, previous studies were unable to link childhood adversity to puberty in boys.

Research published in JAMA Pediatrics by Ying Sun and colleagues examined HCC and pubertal development in 1263 elementary school-aged children (age range 6.4 – 9.9 years) in China. Cortisol was extracted from hair samples and measured using a commercially available cortisol test kit.

For girls, breast development was assessed by the same pediatric endocrinologist using Breast Tanner stages, a scale of physical development. For boys, a Prader orchidometer was used to estimate testicular volume. The study found no difference in cortisol levels between boys and girls. Early breast development was significantly higher for girls with the HCC levels in the third and fourth quartile compared to those with lower HCC levels. Overall, the investigators found a 2.5-fold increase in the risk of early breast development in girls in the highest quartile of HCC compared to those in the lowest quartile.

Similarly, testicular volume in boys was significantly correlated (p< .001) with HCC, those with higher levels of HCC had larger mean testicular volumes. A 0.12-milliliter increase in testicular volume was observed with each quartile increase in HCC in boys.

This is the first study to measure the cortisol level in hair of children in relation to puberty. Scientists hope that additional studies will help us better understand the timing of puberty and how chronic stress increases the risk of early puberty.

Written By: Cindi A. Hoover, Ph.D.

From https://www.medicalnewsbulletin.com/chronic-stress-increases-risk-early-puberty/

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