Phase 2
N=6
Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1
Autosomal Dominant Hypocalcemia (ADH) · Autosomal Dominant Hypocalcemia Type 1 (ADH1)
Bottom Line
View on ClinicalTrials.gov: NCT04581629 ↗Enrolled (actual)
6
Serious AEs
0.0%
Results posted
Nov 2024
Primary outcome: Primary: Periods 1, 2 and 3: Number of Participants With Treatment-emergent Adverse Events (TEAEs) — 5; 13 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Encaleret (Drug)
- Age
- Pediatric, Adult, Older Adult · 16+ yrs
- Sex
- All
- Sponsor
- Calcilytix Therapeutics, Inc., a BridgeBio company
- Primary completion
- Sep 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Periods 1, 2 and 3: Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
5; 13 | — |
| PRIMARY Period 3: Change From Baseline in Albumin-Corrected Blood Calcium Concentrations (cCa) |
1.9 | — |
| PRIMARY Period 3: Rate of Urinary Calcium Excretion |
202 | — |
| SECONDARY Periods 1 and 2: Intact Parathyroid Hormone (iPTH) Concentrations in the Blood |
43.8; 20.6 | — |
| SECONDARY Periods 1 and 2: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Encaleret |
11283.7; 13127.7; 12417.0; 623.7 | — |
| SECONDARY Periods 1, 2 and 3: Maximum Plasma Concentration (Cmax) of Encaleret |
2593.3; 1834.0; 1890.0; 102.0; 223.6; 496.0 | — |
| SECONDARY Periods 1, 2 and 3: Time to Maximum Plasma Concentration (Tmax) of Encaleret |
1.1; 1.5; 2.0; 1.5; 4.0; 1.5 | — |
| SECONDARY Periods 2 and 3: Change From Baseline in Blood Calcium Concentration (cCa) |
1.5; 1.9 | — |
| SECONDARY Period 3: Urinary Calcium Clearance as Assessed by Fractional Excretion |
0.016 | — |
| SECONDARY Periods 1, 2 and 3: Urinary Calcium Clearance as Assessed by 24-Hour Total Excretion |
84; 0; 179; 202 | — |
| SECONDARY Periods 1, 2 and 3: Renal Function as Assessed by Estimated Glomerular Filtration Rate (eGFR) |
91.1; 90.6; 82.0 | — |
| SECONDARY Periods 1, 2 and 3: Serum Levels of 1,25-(OH)2 Vitamin D |
25.8; 30.5; 31.2 | — |
| SECONDARY Periods 1, 2 and 3: Magnesium, Phosphorus, and Creatinine Levels as Assessed by Blood Sample Examinations |
2.2; 1.9; 2.0; 2.9; 3.1; 3.7 | — |
| SECONDARY Periods 1, 2 and 3: Creatinine, Phosphorus, Magnesium, and Citrate Total Excretion Levels as Assessed by Urine Sample Examinations |
1454; 1190; 1408; 1345; 877; 1100 | — |
| SECONDARY Periods 1, 2 and 3: pH as Assessed by Urine Sample Examinations |
6.2; 5.0; 6.1; 6.5 | — |
| SECONDARY Periods 1, 2 and 3: Potassium and Sodium Total Excretion Levels as Assessed by Urine Sample Examinations |
79.00; 82.00; 69.38; 61.46; 186.33; 192.00 | — |
| SECONDARY Periods 1, 2 and 3: Cyclic Adenosine Monophosphate (cAMP) Total Excretion Levels as Assessed by Urine Sample Examinations |
2.98; 2.90; 2.79; 2.68 | — |
| SECONDARY Periods 1, 2 and 3: Bone Resorption Markers as Assessed by Collagen Cross-Linked C-Telopeptide (CTx) |
386; 266; 744 | — |
| SECONDARY Periods 1, 2 and 3: Bone Formation Markers as Assessed by Blood Procollagen Type 1 N-Propeptide (P1NP) |
27.33; 26.8; 103.7 | — |
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.
Data sourced from ClinicalTrials.gov (NCT04581629). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.