Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1

Autosomal Dominant Hypocalcemia (ADH) Clinical Trial

Official title:

A Phase 2b, Open-label Dose-ranging Study Evaluating the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics, and Efficacy of CLTX-305 (Encaleret) in Autosomal Dominant Hypocalcemia (ADH) Type 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04581629
• Other study ID #: CLTX-305-201
• Status: Completed
• Phase: Phase 2
• Start date: September 15, 2020
• Est. completion date: September 7, 2023

Study information

• Verified date: November 2023
• Source: Calcilytix Therapeutics, Inc., a BridgeBio company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to evaluate the safety, tolerability and effectiveness of encaleret in participants with Autosomal Dominant Hypocalcemia Type 1 (ADH1).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: September 7, 2023
• Est. primary completion date: September 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Key Inclusion Criteria:

• Be able to understand and sign a written informed consent or assent form, which must be obtained prior to initiation of study procedures.

• Postmenopausal women are allowed to participate in this study

• Body mass index (BMI) = 18.5 to < 39 kg/m2

• Have an activating mutation of the Calcium-sensing receptor (CASR) gene

• Participants being treated with thiazide diuretics may be enrolled if they are willing and able to discontinue thiazides

• Participants being treated with strong CYP3A4 inhibitors should ideally, if clinically appropriate, discontinue these medications during the screening period

• Participants being treated with magnesium or potassium citrate supplements should discontinue such treatment starting on Day -1 during Period 1 and Period 2 and may be asked to discontinue treatment during Period 3

Key Exclusion Criteria:

• History of treatment with PTH 1-84 or 1-34 within the previous 3 months

• History of hypocalcemic seizure within the past 3 months

• Blood 25-OH Vitamin D level < 25 ng/mL

• Participants with hemoglobin (Hgb) < 13 g/dL for men and < 12 g/dL for women

• Estimated glomerular filtration rate (eGFR) < 25 mL/minute/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (for participants <18 years old the Schwartz equation will be calculated)

• 12-lead resting electrocardiogram (ECG) with clinically significant abnormalities

• Participants with positive hepatitis B surface antigen (HBsAg), hepatitis A immunoglobulin M (IgM), or human immunodeficiency virus (HIV) viral serology test results at the Screening Visit

• Pregnant or nursing (lactating) women

• History of drug or alcohol dependency within 12 months preceding the Screening Visit

• History of thyroid or parathyroid surgery

• Current participation in other investigational drug studies

• Unwillingness to refrain from blood donation within 12 weeks prior to Screening Visit from the start of the study enrollment through one year after the last dose of the study drug

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Arthrogryposis
• Autosomal Dominant Hypocalcemia (ADH)
• Hypocalcemia

Intervention

Drug:
• Encaleret
Tablets administered orally

Locations

Country	Name	City	State
United States	National Institute of Health	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Calcilytix Therapeutics, Inc., a BridgeBio company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AEs)		Up to 3 years
Primary	Change From Baseline in Albumin-Corrected Blood Calcium Concentrations (cCa)		Up to 25 weeks
Primary	Rate of Urinary Calcium Excretion		Predose, Up to 24 hours postdose
Secondary	Change From Baseline in Intact Parathyroid Hormone (iPTH) Concentration in Blood		Predose, Up to 24 hours postdose
Secondary	Area Under the Concentration-Time Curve Etrapolated to infinity (AUC0-inf)		Predose, Up to 24 hours postdose
Secondary	Maximum Plasma Concentration (Cmax)		Predose, Up to 24 hours postdose
Secondary	Time to Maximum Plasma Concentration (Tmax)		Predose, Up to 24 hours postdose
Secondary	Change From Baseline in Blood Calcium Concentration (cCa)		Up to 3 years
Secondary	Urinary Calcium Clearance as Assessed by Fractional Excretion		Up to 3 years
Secondary	Urinary Calcium Clearance as Assessed by 24-Hour Total Excretion		Up to 3 years
Secondary	Renal Function as Assessed by Estimated Glomerular Filtration Rate (eGFR)		Up to 3 years
Secondary	Serum levels of 1,25-(OH)2 Vitamin D		Up to 3 years
Secondary	Magnesium, Phosphate, Creatinine Levels as Assessed by Blood Sample Examinations		Up to 3 years
Secondary	PH, Magnesium, Phosphate, Sodium, Potassium, Creatinine, cyclic adenosine monophosphate (cAMP), Citrate Levels as Assessed by Urine Sample Examinations		Up to 3 years
Secondary	Bone Resorption Markers as Assessed by Collagen Cross-Linked C-Telopeptide (CTx)		Up to 3 years
Secondary	Bone Formation Markers as Assessed by Blood Procollagen Type 1 N-Propeptide (P1NP)		Up to 3 years