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Evaluate the Safety, effectiveness and action of CRN04894 in the body in Participants with Congenital Adrenal Hyperplasia.

Phase 2
Conditions
Health Condition 1: E250- Congenital adrenogenital disordersassociated with enzyme deficiency
Registration Number
CTRI/2023/12/060825
Lead Sponsor
Crinetics Pharmaceuticals Inc.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Yet Recruiting
Sex
Not specified
Target Recruitment
0
Inclusion Criteria

1.Willing and able to understand and adhere to the study procedures.

2.Classic 21-hydroxylase deficiency confirmed by the Investigator and approved by the

Medical Monitor.

3.The A4 and 17-OHP values taken before morning glucocorticoid (GC) dose during

Screening Visit 2 (at Week-2), should meet these criteria:

a.A4 more than 1.5 X upper limit of normal (ULN) and

b.17-OHP more than or equal to 1000 ng/dL (30.3 nmol/L); historical results from within the last 2 years will be accepted if the participant has been on the current dose of GC since that time.

Participants who failed screening based on findings the Investigator believes are

temporary and not reflective of the usual state of the participant (eg, normal A4 levels

when the participant usually is well above this value) can be considered for rescreening.

These cases should be discussed with the Medical Monitor.

4.On a stable (defined as no dose change of more than 5 mg/day hydrocortisone equivalent within 6 months prior to Screening) regimen of glucocorticoid replacement (eg, hydrocortisone, prednisolone, prednisone, methylprednisolone).

5.Compliance, as judged per principal investigator (PI) discretion, with glucocorticoid

replacement and mineralocorticoid replacement (if applicable) regimen documented

during the Screening Period.

6.Minimum total daily dose of more than or equal to 15 mg hydrocortisone (or equivalent).

7.If on estrogen therapy (any route), dose must be stable for at least 3 months prior to

Screening.

8.Female participants who engage in heterosexual intercourse must be of nonchildbearing

potential, defined as either surgically sterile (ie, hysterectomy, bilateral salpingectomy,

tubal ligation for at least 3 months, or bilateral oophorectomy), or be postmenopausal

with at least 1 year of amenorrhea. In participants with less than 1 year of amenorrhea

confirmation of a follicle stimulating hormone (FSH) more than or equal to 30 IU/L is required to confirm menopause. Participants not using hormone replacement therapy must agree to use a highly effective method of contraception from the beginning of Screening until at least 2 weeks after the last dose of study drug. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those

participating in clinical studies. Periodic abstinence (ie, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.

9.Male participants: The participant should agree to use a condom when sexually active

with a female partner of childbearing potential from Screening until at least 2 weeks after

the last dose of study drug (or be surgically sterile [ie, vasectomy with a confirmed

absence of sperm in ejaculate]); or agree to remain abstinent on a long term and persistent

basis). Male participants should also agree to not donate sperm for the duration of the

study and until at least 2 weeks after the last dose of study drug.

Exclusion Criteria

1. Diagnosis of any other form of CAH other than classic 21-hydroxylase deficiency

2. Dexamethasone use within 30 days of screening

3. History of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic

glucocorticoid therapy

4. Night shift workers or any other reason for abnormal sleep/wake cycles

5. Clinically significant unstable medical condition or chronic disease other than CAH

6. History of major surgery/surgical therapy for any cause within 4 weeks prior to Screening

7. Diabetes mellitus treated with insulin for less than 6 weeks prior to Screening, or with

change in total daily insulin dose by more than 15 percent within 6 weeks prior to Screening

8. Poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) more than or equal to 8.5 percent (more than or equal to 69 mmol/mL), or estimated HbA1c based on fructosamine if HbA1c is not evaluable (eg, due to hemoglobinopathies)

9. Participants with hypothyroidism who are not receiving adequate hormone replacement

therapy based on thyroid hormone levels measured at the time of Screening, as

determined by the Investigator.

10. History of unstable angina or acute myocardial infarction within 12 weeks prior to

Screening or other clinically significant cardiac disease at the time of Screening as judged

by the Investigator

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. History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or

cervical carcinoma in situ

13. Pregnant or lactating

14. Known history of illicit drug or alcohol abuse within the last year

15. Use of antiandrogen therapy in the past 3 months (eg, spironolactone, finasteride,

cyproterone acetate, flutamide)

16. Use of testosterone, androgen-containing supplements, aromatase inhibitors, or growth

hormone

17. Use of medications that are strong inducers of cytochrome P450 (CYP) 3A4 within

30 days prior to Day 1 of the study. These include but are not limited to apalutamide,

carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, or St. John’s wort.

18. Use of medications (all routes of administration ie, oral, topical and inhaled) or ingestion

of food that are strong or moderate inhibitors of CYP3A4 within 14 days prior to Day 1

of the study. These include but are not limited to boceprevir, cobicistat, danoprevir and

ritonavir, elvitegravir and ritonavir, grapefruit juice (more than 8 ounces daily), indinavir

and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, nirmatrelvir and

ritonavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole,

ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, telithromycin,

troleandomycin, voriconazole, clarithromycin, idelalisib, nefazodone, nelfinavir,

aprepitant, ciprofloxacin, conivaptan, crizotinib, cyclosporine, diltiazem, dronedarone,

erythromycin, fluconazole, fluvoxamine, imatinib, tofisopam, verapamil.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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