AZP-3601 SAD and MAD Study in Healthy Subjects and Patients With Hypoparathyroidism

Chronic Hypoparathyroidism Clinical Trial

Official title:

A Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZP-3601, a Synthetic Parathyroid Hormone Analog, in Healthy Subjects and in Subjects With Hypoparathyroidism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05239221
• Other study ID #: AZP-3601-CLI-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 7, 2020
• Est. completion date: August 23, 2022

Study information

• Verified date: January 2024
• Source: Amolyt Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is investigating the safety, tolerability, pharmacodynamics and pharmacokinetics of AZP-3601 following single and repeated administration in both healthy volunteers and patients with chronic hypoparathyroidism (cHP)

The protocol includes 3 parts:

• Part A: first-in-human single ascending dose (SAD) study in healthy volunteers

• Part B: multiple ascending dose (MAD) study with 2 weeks of treatment in healthy volunteers

• Part C: open-label MAD study with a total treatment duration of 3 months in patients with cHP.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: August 23, 2022
• Est. primary completion date: August 23, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Main inclusion criteria

• Part A: healthy male volunteers aged 18 to 60 years old inclusive with a body mass index of 19 to 28 kg/m2

• Part B: healthy male and female volunteers (non-child bearing potential) aged 18 to 60 years inclusive with a Body mass index of 19 to 28 kg/m2

• Part C:

1. Male and female patients aged 18 to 75 years inclusive

2. History of cHP for =12 months at the time of screening with documentation of two measurements of serum calcium and parathyroid hormone (PTH).

3. Requirement for therapy with calcitriol =0.25 µg per day or alphacalcidol =0.50 µg per day (both are active vitamin D supplements), and requirement for supplemental oral calcium treatment =1000 mg per day over and above normal dietary calcium intake at baseline assessments.

Main exclusion criteria

• Parts A and B:

1. Clinically significant abnormal lab values, as judged by the investigator

2. Using tobacco products with 3 months prior to first drug administration

3. History of alcohol abuse or drug addiction

• Part C:

1. Known history of autosomal-dominant hypocalcemia (ADH resulting from gain-of-function calcium-sensing receptor [CaSR] or GNA11 mutations) or pseudohypoparathyroidism (impaired responsiveness to PTH)

2. Any current disease that might affect calcium metabolism or calcium phosphate homeostasis other than HP

3. Use of medications such as loop and thiazide diuretics, raloxifene hydrochloride, lithium, methotrexate, cardiac glycosides (e.g., digoxin or digitoxin) or systemic corticosteroids within 4 weeks prior to start of treatment.

4. Previous treatment with PTH-like drugs, including PTH(1-84), PTH(1-34), or abaloparatide, within 3 months prior to screening.

Related Conditions & MeSH terms

• Chronic Hypoparathyroidism
• Hypoparathyroidism

Intervention

Drug:
• AZP-3601
Lyophilized powder of AZP-3601 to be reconstituted with water for injection before injection
• Placebo
Saline solution visually matching active medication

Locations

Country	Name	City	State
Hungary	Amolyt Pharma Investigational Site Hungary	Budapest
Netherlands	PRA-EDS	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Amolyt Pharma

Countries where clinical trial is conducted

Hungary,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Calcium Excretion Rate 24h- Part C	24 hour calcium excretion rate (mg/24h) in Part C.	Day 1, Day 14, Day 28 and Day 84
Primary	Treatment Emergent Adverse Events (TEAEs)	Number of Treatment Emergent Adverse Events (TEAEs), as assessed by medDRA (v25).	Up to 2 weeks in Part A and Part B, and up to 3 months in Part C
Secondary	Observed Maximum Concentration (Cmax) - Part A	Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part A	24 hours
Secondary	Observed Maximum Concentration (Cmax) - Part B	Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part B	Day 1, Day 14
Secondary	Observed Maximum Concentration (Cmax) - Part C	Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part C.	Day 1, Day 14, Day 28, Day 84
Secondary	Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A	Area under the plasma-drug concentration time curve (AUC) (pg*h/mL) in Part A	24 hours
Secondary	Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B	Area Under the Plasma-drug Concentration Time Curve (AUC) (pg*h/mL) in Part B	Day 1, Day 14
Secondary	Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C	Area Under the Plasma-drug Concentration Time Curve (AUC) (pg*h/mL) in Part C.	Day 1, Day 14, Day 28, Day 84
Secondary	Calcium Corrected for Albumin - Part A	Levels of calcium corrected for albumin (mg/dL) in Part A	24 hours
Secondary	Calcium Corrected for Albumin - Part B	Levels of calcium corrected for albumin (mg/dL) in Part B	24 hours, Day 14
Secondary	Calcium Corrected for Albumin - Part C	Levels of calcium corrected for albumin (mg/dL) in Part C.	Day 1, Day 14, Day 28 and Day 84
Secondary	Serum Phosphate - Part A	Serum phosphate levels (mg/dL) in Part A	24 hours
Secondary	Serum Phosphate - Part B	Serum phosphate levels (mg/dL) in Part B	Day 1, Day 14
Secondary	Serum Phosphate - Part C	Serum phosphate levels (mg/dL) in Part C.	Day 1 (H0), Day 14 (H2), Day 28 (H2) and Day 84 (H2)
Secondary	Daily Dose of Oral Calcium and Active Vitamin D - Part C	Daily dose of oral calcium and active vitamin D for patients treated in Part C.	Day 28 and Day 43