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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chronic Hypoparathyroidism

Intervention / Treatment
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* Drug: AZP-3601
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main inclusion criteria Part A: healthy male volunteers aged 18 to 60 years 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: Male and female patients aged 18 to 75 years inclusive History of cHP for ≥12 months at the time of screening with documentation of two measurements of serum calcium and parathyroid hormone (PTH). 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: Clinically significant abnormal lab values, as judged by the investigator Using tobacco products with 3 months prior to first drug administration History of alcohol abuse or drug addiction Part C 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) Any current disease that might affect calcium metabolism or calcium phosphate homeostasis other than HP 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. Previous treatment with PTH-like drugs, including PTH(1-84), PTH(1-34), or abaloparatide, within 3 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZP-3601<br>s.c. administration once daily | Drug: AZP-3601<br>* Lyophilized powder of AZP-3601 to be reconstituted with water for injection before injection<br>|
| Placebo Comparator: Placebo (Parts A and B)<br>s.c. administration once daily | Drug: Placebo<br>* Saline solution visually matching active medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent Adverse Events (TEAEs) | Number of TEAEs as assessed by medDRA | up to 2 weeks (Parts A and B), up to 3 months (Part C) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of AZP-3601 |  | Day 1 (all Parts), Day 14 (Parts B and C), Day 28 (Part C) | 
| Serum calcium |  | up to 2 weeks (Parts A and B), up to 3 months (Part C) | 
| Serum phosphorus |  | up to 2 weeks (Parts A and B), up to 3 months (Part C) | 
| s-CTx | serum carboxy-terminal telopeptide of type I collagen (bone turnover biomarker) | up to 2 weeks (Part B), up to 3 months (Part C) | 
| P1NP | serum procollagen type 1 amino-terminal propeptide (bone turnover biomarker) | up to 2 weeks (Part B), up to 3 months (Part C) | 
| Daily dose of oral calcium and active vitamin D (Part C) |  | up to 3 months (Part C) |