E220 Acromegaly and pituitary gigantism Acromegaly and pituitary gigantism
Conditions
Interventions
The study comprises 2 phases: an RC phase and long-term OLE phase. Subjects who participate in both phases will complete approximately 144 weeks (almost 3 years) of treatment and observation. The stud
Week -12 through Day -1 (There are 2 to 3 visits during the Screening Period)
• RC phase: 36 weeks
- Treatment Period: Day 1 through Week 36 with up to 13 planned visits
the end of Week 36 is the last planned visit of the RC phase and is defined as EOR
- Week 1 through Week 24 will be the dose Titration Period
• OLE: 96 weeks
- 9 planned visits (1 visit approximately
the end of 96 weeks of the OLE phase is the planned EOT
- EOS: Defined as the day final study data are collected and should occur 4 weeks after the last dose of study drug
the end of the Week 136/EOS is the last planned visit of the study (Follow-up Visit), but EOS could occur at Week 40 in subjects who do not enter the OLE
• Subjects who withdraw consent or are permane
Week -12 through Day -1 (There are 2 to 3 visits during the S
Sponsors
Crinetics Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Willing and able to provide written informed consent prior to any study-related procedures. (2) Willing and able to comply with the study procedures as specified in the protocol and comply the study treatment administration. Demographics and Medical History. (3) Adults =18 years of age with medically stable, confirmed-active acromegaly and on an approved, stable dose of long-acting octreotide or lanreotide, for at least 12 weeks prior to Screening*. Continuous treatment with octreotide or lanreotide monotherapy must be at least 24 weeks prior to Screening. *The following prior treatment regimens are allowed for inclusion into this study: long-acting octreotide: 10, 20, 30, 40 mg every 4 weeks or long-acting lanreotide: 60, 90, 120 mg every 4 weeks or 120 mg every 6 or 8 weeks. (4) Previous diagnosis of acromegaly confirmed by the Investigator and approved by the Medical Monitor. This requires evaluable documentation of a pituitary tumor diagnosed by pituitary imaging or histopathologic confirmation of a pituitary adenoma at least 24 weeks prior to Screening. For subjects who have had pituitary surgery, there must be documentation of IGF-1 concentration =1.3×ULN at least 12 weeks after last pituitary surgery. The surgery must have been performed =24 weeks prior to Screening. Subjects who have not had pituitary surgery must have documentation of IGF-1 concentration =1.3×ULN performed =24 weeks prior to Screening. Screening and Testing Evaluations. (5) Screening average IGF-1 levels of =1.0×ULN. Average IGF-1 (rounded to 2 decimal places or =1.04) will be based on 2 or 3 separate measurements in consultation with the Medical Monitor. (6) Willing and able to undergo biliary/gallbladder ultrasound procedure during Screening and during the study. (7) If currently using thyroid hormone therapy, the subject should be adequately treated based on clinical status and free thyroxine concentration measured during Screening and on a stable dose of thyroid hormone for at least 4 weeks prior to Screening. Lifestyle Restrictions. (8) Females who engage in heterosexual intercourse must be of non childbearing potential, defined as either surgically sterile (i.e., hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), OR be postmenopausal with at least 1 year of amenorrhea, OR must agree to use either a highly effective or a clinically acceptable method of contraception from the beginning of Screening to the last study visit. • Acceptable highly effective methods of contraception include: - Non cyclic, stable dose (monophasic) combined estrogen-progestin oral hormonal contraception associated with consistent inhibition of ovulation. Oral contraceptives containing estrogens should be in stable use for at least 12 weeks prior to Screening. - Desogestrel based progestin only contraception associated with consistent inhibition of ovulation; this includes oral, injectable, and implantable methods - Intravaginal and transdermal hormone delivery methods - Intrauterine device (with or without hormone elution) - Bilateral tubal occlusion or ligation (must be documented) - Vasectomized partner (must be documented) or - Sexual abstinence (only when it is the usual and preferred lifestyle of the subject) • Clinically acceptable methods of birth control include: - Male or female condom with or without spermicide; - Norethindrone-based progestin-only oral co
Exclusion criteria
Exclusion criteria: Medical History and Medications (1) Treatment-naïve or treatment-withdrawn acromegaly subjects. (2) History of pituitary radiation therapy. (3) Subjects with adrenal insufficiency who are not receiving adequate adrenal replacement therapy at the time of Screening, as determined by the Investigator. (4) High risk pituitary tumor pattern as defined by: • Compression of the optic chiasm or invasion of adjacent brain structures (other than sphenoid sinus or cavernous sinus) • History of tumor growth within 1 year after surgery or radiation (unless it occurred during a period of medical therapy interruption) • Anticipated requirement for neurosurgical intervention or radiation therapy within the time course of the study. • Pituitary carcinoma currently or at any time in the past. (5) History of major surgery/surgical therapy for any cause within 4 weeks prior to Screening. (6) Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry, or with change in total daily insulin dose by >15% within 6 weeks prior to Screening. (7) History of unstable angina or acute myocardial infarction within the 12 weeks preceding the screening visit or other clinically significant cardiac disease at the time of screening as judged by the Investigator. (8) Known history of hepatitis B or human immunodeficiency virus, or active hepatitis C infection. (9) Known history of, or current alcohol or drug abuse, within the last year. (10) Active malignant disease within the last 5 years with exception of basal and squamous cell carcinoma of the skin with complete local excision and resected carcinoma in situ of cervix. (11) Concomitant mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study, and/or evidence of poor compliance with medical instructions. (12) Use of the following medications as outlined: • Pasireotide LAR (within 24 weeks prior to Screening), • Pegvisomant (within 12 weeks before Screening), • Dopamine agonists (within 12 weeks before Screening), or • Short acting somatostatin analogs (SA-SSAs) within last 12 weeks before the first dose of study drug. Note: Withdrawal of these medications should be part of the subject’s medical care plan prior to Screening; entry into the study should not be the sole reason for withdrawal of a prior medication. (13) Current use of oral estrogen replacement therapy for 160 mmHg and/or su
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects who maintain biochemical response in IGF 1 (=1.0×the upper limit of normal [ULN]) at the End of the Randomized Control Phase (EOR). NAME OF THE RESULT: To evaluate the effect of paltusotine versus placebo on IGF 1 response. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At the End of the Randomized Control Phase (EOR). | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects who maintain biochemical response in IGF 1 (=1.0×the upper limit of normal [ULN]) at the End of the Randomized Control Phase (EOR). NAME OF THE RESULT: To evaluate the effect of paltusotine versus placebo on IGF 1 response. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At the End of the Randomized Control Phase (EOR). ;Change from baseline in IGF-1, in units of ULN, to EOR. NAME OF THE RESULT: To evaluate the effect of paltusotine versus placebo on IGF 1 level. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From baseline to EOR. ;Proportion of subjects with GH <1.0 ng/mL at Week 34, out of those who had GH <1.0 ng/mL at Screening. NAME OF THE RESULT: To evaluate the effect of paltusotine versus placebo on GH response. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Week 34. ;Change from baseline in Total Acromegaly Symptoms Diary (ASD) score to EOR. NAME OF THE RESULT: To evaluate the effect of paltusotine versus placebo on acromegaly symptoms. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From baseline to EOR. | — |
Countries
Belgium, Brazil, Bulgaria, France, Italy, Poland, Serbia, United Kindgdom, United States
Contacts
Public ContactSARA ROCIO DE LOS MILAGROS TUME
RESOLUTION LATIN AMERICA PERU SOCIEDAD ANONIMA - RESOLUTION LATIN AMERICA PERU S.A.
Outcome results
None listed