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Completed

NCT Number: NCT04581629

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

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).

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Key information

Conditions

Autosomal Dominant Hypocalcemia (ADH) Autosomal Dominant Hypocalcemia Type 1 (ADH1) Hypercalciuric Hypocalcemia, Familial

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

National Institutes of Health (NIH) Clinical Center

Bethesda, Maryland, 20892, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

encaleret

Drug

Tablets administered orally

Other names: CLTX-305

Primary outcomes

  1. Periods 1, 2 and 3: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    Time frame: Day 1 up to 16 months

    Adverse events (AEs) were defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Treatment-emergence was defined as any AE(s) regardless of relationship to investigational medicinal product (IMP), that had an onset or worsened in severity on or after the first dose of IMP.

  2. Period 3: Change From Baseline in Albumin-Corrected Blood Calcium Concentrations (cCa)

    Time frame: Baseline, Week 24

  3. Period 3: Rate of Urinary Calcium Excretion

    Time frame: Week 24

Secondary outcomes

  1. Periods 1 and 2: Intact Parathyroid Hormone (iPTH) Concentrations in the Blood

    Time frame: 15 minutes pre-dose on Day 5 of Periods 1 and 2 (Periods were 5 days)

    Blood samples were taken for analysis of iPTH concentrations. iPTH concentrations were analyzed via an electrochemiluminescence immunoassay.

  2. Periods 1 and 2: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Encaleret

    Time frame: Periods 1 and 2: Day 5 (Periods were 5 days)

  3. Periods 1, 2 and 3: Maximum Plasma Concentration (Cmax) of Encaleret

    Time frame: Periods 1 and 2: Day 5, Period 3: Week 24 (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)

  4. Periods 1, 2 and 3: Time to Maximum Plasma Concentration (Tmax) of Encaleret

    Time frame: Periods 1 and 2: Day 5; Period 3: Week 24 (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)

  5. Periods 2 and 3: Change From Baseline in Blood Calcium Concentration (cCa)

    Time frame: Period 2: Baseline, Day 5 (Period was 5 days), Period 3: Baseline, Week 24 (Period was 24 weeks)

    Data values presented are for the change from baseline for the average values at the specified timepoints/visits.

  6. Period 3: Urinary Calcium Clearance as Assessed by Fractional Excretion

    Time frame: Period 3: Week 24, 15 minutes pre-dose (Period was 24 weeks)

    Fractional Excretion of Calcium was derived as (Urine Calcium at the interval considered * Serum Creatinine at the end of the interval considered)/(Serum Calcium at the end of the interval considered * Urine Creatinine at the interval considered) and is presented as percentage.

  7. Periods 1, 2 and 3: Urinary Calcium Clearance as Assessed by 24-Hour Total Excretion

    Time frame: Periods 1 and 2: Day 5; Period 3, Week 24 (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)

  8. Periods 1, 2 and 3: Renal Function as Assessed by Estimated Glomerular Filtration Rate (eGFR)

    Time frame: 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)

    eGFR was calculated using Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) formula (mL/min/1.73m^2) = 141 x min (SCr/K, 1)^α x max(SCR /K,1)-1.209 x 0.993Age x 1.018 [if female] x 1.159 [if Black], where SCr is the serum creatinine (mg/dL), K = 0.7 for female and 0.9 for males, α is -0.329 for female and -0.411 for males.

  9. Periods 1, 2 and 3: Serum Levels of 1,25-(OH)2 Vitamin D

    Time frame: 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)

  10. Periods 1, 2 and 3: Magnesium, Phosphorus, and Creatinine Levels as Assessed by Blood Sample Examinations

    Time frame: 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)

  11. Periods 1, 2 and 3: Creatinine, Phosphorus, Magnesium, and Citrate Total Excretion Levels as Assessed by Urine Sample Examinations

    Time frame: 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)

  12. Periods 1, 2 and 3: pH as Assessed by Urine Sample Examinations

    Time frame: 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)

  13. Periods 1, 2 and 3: Potassium and Sodium Total Excretion Levels as Assessed by Urine Sample Examinations

    Time frame: 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)

  14. Periods 1, 2 and 3: Cyclic Adenosine Monophosphate (cAMP) Total Excretion Levels as Assessed by Urine Sample Examinations

    Time frame: 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)

  15. Periods 1, 2 and 3: Bone Resorption Markers as Assessed by Collagen Cross-Linked C-Telopeptide (CTx)

    Time frame: 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)

    Blood samples were taken for analysis of bone resorption markers (CTx).

  16. Periods 1, 2 and 3: Bone Formation Markers as Assessed by Blood Procollagen Type 1 N-Propeptide (P1NP)

    Time frame: 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)

    Blood samples were taken for analysis of bone formation markers (P1NP).

Sponsors and collaborators

Lead sponsor

Calcilytix Therapeutics, Inc., a BridgeBio company

Industry

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Oct 9, 2020
Registry last updated
Nov 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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