Safety, Tolerability, Pharmacodynamics and Pharmacokinetics, and Efficacy of CLTX-305 in Autosomal Dominant Hypocalcemia Type 1 (ADH1)

Hypoparathyroidism Clinical Trial

Official title: A Phase IIb, Open-label Dose-ranging Study Evaluating the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics, and Efficacy of CLTX Hypocalcemia Type l (ADHl).

Status Not yet recruiting

Clinical Trial Summary

Background:

The Calcium-Sensing Receptor (CaSR) detects the amount of calcium in the blood and urine. Parathyroid hormone (PTH) helps keep blood calcium levels normal. When PTH and calcium blood levels are low, this is called hypoparathyroidism. People with changes in the CaSR have a type of hypoparathyroidism called ADH1. ADH1 is treated with calcium supplements and vitamin D. But these do not always work, and can cause problems like kidney stones. Researchers want to see if the drug CLTX-305 is a better treatment option.

Objective:

To see if CLTX-305 is safe and works in people with ADH1.

Eligibility:

People ages 16 and older with ADH1

Design:

Participants will be screened with:

Medical history

Physical exam

Kidney ultrasound: Participants will lie on a table while a wand is moved over their back.

Bone density test: Participants will lie on a table while an X-ray machine moves around them.

Blood, urine, and heart tests

The study is split into 3 periods. Participants may take part in some or all periods.

In Periods 1 and 2, participants will take CLTX-305 by mouth once or twice daily for up to 5 days. Participants will stay at the NIH for 7 days and 6 nights.

In Period 3, participants will take CLTX-305 at home for 24 weeks. They will have 3 inpatient visits that last 1 2 days each.

Screening tests will be repeated during the study. Blood and urine will be collected often.

Participants dose of calcium and vitamin D may be changed. They may be asked to stop taking other medicines or change the dose.

Clinical Trial Description

Study Description:

This will be a single-site, open-label, dose-ranging study to evaluate the safety, tolerability and efficacy of CLTX-305 to maintain normalized albumin-corrected blood calcium (cCa) in subjects with hypocalcemia due to ADH1. The study consists of 2 cohorts and 3 periods.

Primary Objectives:

• Periods 1 and 2: Evaluate the safety and tolerability of single and multiple doses of CLTX-305 in subjects with ADH1

• Period 3: Evaluate the efficacy of CLTX-305 in subjects with ADH1 after 24 weeks of dosing

Secondary Objectives:

• Periods 1 and 2:

--Evaluate the effect of CLTX-305 to increase serum PTH levels after both single and multiple doses across a dose range in subjects with ADH1

• Periods 1, 2, and 3:

• Evaluate the pharmacodynamic (PD) effects of CLTX-305 on blood calcium concentrations

• Evaluate the PD effects of CLTX-305 on associated measures of calcium homeostasis including 1,25-(OH)2 vitamin D levels and urinary calcium excretion

• Evaluate the PK of both single and multiple ascending doses of CLTX-305 in subjects with ADH1.

• Period 3:

• Evaluate the safety and tolerability of CLTX-305 in subjects with ADH1 after 24 weeks of dosing

Primary Endpoints:

• Periods 1 and 2: Adverse events (AEs), clinical safety laboratory tests, vital signs, and electrocardiograms (ECGs)

• Period 3: Albumin-corrected blood calcium concentrations (cCa) after treatment with CLTX-305 for up to 24 weeks.

Secondary Endpoints:

• Periods 1 and 2: iPTH blood concentrations profiles (24-hours) over time after single and multiple doses of CLTX-305

• Period 3: AEs, clinical safety laboratory tests, vital signs, and ECGs

• Periods 1, 2, and 3:

• Pharmacodynamic endpoints measured over time up to 24 weeks (final visit):

• Blood calcium - Absolute levels and change from baseline in cCa

• Urinary calcium clearance (fractional excretion and 24-hour total excretion)

• Serum levels of 1,25-(OH)2 Vitamin D

• Blood samples for magnesium, phosphate, creatinine

• Urine samples for pH, magnesium, phosphate, sodium, potassium, creatinine, cAMP, citrate

• Bone resorption markers collagen cross-linked C-telopeptide (CTx)

• Bone formation markers blood procollagen type 1 N-propeptide (P1NP)

• PK parameters: maximum plasma concentration (Cmax), time to maximum plasma concentration (tmax), apparent terminal half-life (t1/2), area under the concentration-time curve (AUC) from time 0 to the last measurable time point (AUC(0-t)), AUC from time 0 to 24 hours (AUC(0-24)), AUC extrapolated to infinity (AUC(0-inf)) following single-doses.

• Determination of the steady state PK parameters: Cmax, trough concentration (Ctrough), and AUC over the dosing interval AUC(0-tau)

Study Population:

Up to 20 male or female subjects (16 to enter the treatment phase) with Autosomal Dominant Hypocalcemia Type 1(ADH1)

Phase: Phase 2b

Description of Sites/Facilities Enrolling Participants:

National Institutes of Health (NIH) Clinical Center (CC)

Description of Study Intervention:

CLTX-305 is an oral tablet containing the active ingredient encaleret provided in 10, 30 and 60 mg doses.

Study Duration:

Estimated time from when the study opens to enrollment until completion of data analyses is approximately 24 months.

Participant Duration:

Total duration of study participation, including Periods 1, 2, and 3, will be approximately 12 months for each subject, including up to 60 days between the screening visit and study drug initiation. ;

Related Conditions & MeSH terms

• Hypocalcemia
• Hypoparathyroidism

• NCT number: NCT04465227
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Karen A Pozo, R.N.
• Phone: (301) 827-1138
• Email: karen.pozo@nih.gov
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 15, 2020
• Completion date: September 30, 2021