Clinical trial NCT04581629: Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autosomal Dominant Hypocalcemia (ADH)
Autosomal Dominant Hypocalcemia Type 1 (ADH1)
Lead sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company
Sponsor class: INDUSTRY
First posted: 2020-10-09
Enrollment: 13
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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 kilograms (kg)/square meter (m\^2)
* 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 Cytochrome P3A4 (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 parathyroid hormone (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 nanograms (ng)/milliliter (mL)
* Participants with hemoglobin (Hgb) \< 13 grams (g)/deciliter (dL) for men and \< 12 g/dL for women
* Estimated glomerular filtration rate (eGFR) \< 25 mL/minute/1.73 m\^2 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.

Primary outcomes:
measure: Periods 1, 2 and 3: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to 16 months
measure: Period 3: Change From Baseline in Albumin-Corrected Blood Calcium Concentrations (cCa)
timeFrame: Baseline, Week 24
measure: Period 3: Rate of Urinary Calcium Excretion
timeFrame: Week 24
Secondary outcomes:
measure: Periods 1 and 2: Intact Parathyroid Hormone (iPTH) Concentrations in the Blood
timeFrame: 15 minutes pre-dose on Day 5 of Periods 1 and 2 (Periods were 5 days)
measure: Periods 1 and 2: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Encaleret
timeFrame: Periods 1 and 2: Day 5 (Periods were 5 days)
measure: Periods 1, 2 and 3: Maximum Plasma Concentration (Cmax) of Encaleret
timeFrame: Periods 1 and 2: Day 5, Period 3: Week 24 (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 1, 2 and 3: Time to Maximum Plasma Concentration (Tmax) of Encaleret
timeFrame: Periods 1 and 2: Day 5; Period 3: Week 24 (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 2 and 3: Change From Baseline in Blood Calcium Concentration (cCa)
timeFrame: Period 2: Baseline, Day 5 (Period was 5 days), Period 3: Baseline, Week 24 (Period was 24 weeks)
measure: Period 3: Urinary Calcium Clearance as Assessed by Fractional Excretion
timeFrame: Period 3: Week 24, 15 minutes pre-dose (Period was 24 weeks)
measure: Periods 1, 2 and 3: Urinary Calcium Clearance as Assessed by 24-Hour Total Excretion
timeFrame: Periods 1 and 2: Day 5; Period 3, Week 24 (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 1, 2 and 3: Renal Function as Assessed by Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Periods 1 and 2: Day 5 (15 minutes pre-dose), Period 3: Week 24 (15 minutes pre-dose) (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 1, 2 and 3: Serum Levels of 1,25-(OH)2 Vitamin D
timeFrame: Periods 1 and 2: Day 5 (15 minutes pre-dose), Period 3: Week 24 (15 minutes pre-dose); (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 1, 2 and 3: Magnesium, Phosphorus, and Creatinine Levels as Assessed by Blood Sample Examinations
timeFrame: Periods 1 and 2: Day 5 (15 minutes pre-dose), Period 3: Week 24 (15 minutes pre-dose); (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 1, 2 and 3: Creatinine, Phosphorus, Magnesium, and Citrate Total Excretion Levels as Assessed by Urine Sample Examinations
timeFrame: Periods 1 and 2: Day 5 (0-24h post-dose), Period 3: Week 24 (0-24h post-dose); (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 1, 2 and 3: pH as Assessed by Urine Sample Examinations
timeFrame: Periods 1 and 2: Day 5 (0-24 hours post-dose), Period 3: Week 24: (0-24 hours post-dose); (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 1, 2 and 3: Potassium and Sodium Total Excretion Levels as Assessed by Urine Sample Examinations
timeFrame: Periods 1 and 2: Day 5 (0-24h post-dose), Period 3: Week 24 (0-24h post-dose); (Period was 5 days for periods 1 and 2; 24 weeks for period 3)
measure: Periods 1, 2 and 3: Cyclic Adenosine Monophosphate (cAMP) Total Excretion Levels as Assessed by Urine Sample Examinations
timeFrame: Periods 1 and 2: Day 5 (0-4h post-dose), Period 3: Week 24 (0-4h post dose); (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 1, 2 and 3: Bone Resorption Markers as Assessed by Collagen Cross-Linked C-Telopeptide (CTx)
timeFrame: Periods 1 and 2: Day 5 (15 minutes pre-dose), Period 3 Week 24 (15 minutes pre-dose); (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
measure: Periods 1, 2 and 3: Bone Formation Markers as Assessed by Blood Procollagen Type 1 N-Propeptide (P1NP)
timeFrame: Periods 1 and 2: Day 5 (15 minutes pre-dose), Period 3 Week 24 (15 minutes pre-dose); (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health (NIH) Clinical Center
state: Maryland
Study officials:
affiliation: Calcilytix Therapeutics, Inc., a BridgeBio company
name: Calcilytix Medical Director
role: STUDY_DIRECTOR
References: