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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hypoparathyroidism
• Intervention / Treatment: Drug: AZP-3601; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary
    • Amolyt Pharma Investigational Site Hungary
• Netherlands
  • Groningen, Netherlands, 9728
    • PRA-EDS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZP-3601; subcutaneous (sc) administration once daily	Drug: AZP-3601; Lyophilized powder of AZP-3601 to be reconstituted with water for injection before injection; Other Names: eneboparatide
Placebo Comparator: Placebo (Parts A and B); subcutaneous (sc) administration once daily	Drug: Placebo; Saline solution visually matching active medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed Maximum Concentration (Cmax) - Part A	Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part A	24 hours
Observed Maximum Concentration (Cmax) - Part B	Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part B	Day 1, Day 14
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
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
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
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
Calcium Corrected for Albumin - Part A	Levels of calcium corrected for albumin (mg/dL) in Part A	24 hours
Calcium Corrected for Albumin - Part B	Levels of calcium corrected for albumin (mg/dL) in Part B	24 hours, Day 14
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
Serum Phosphate - Part A	Serum phosphate levels (mg/dL) in Part A	24 hours
Serum Phosphate - Part B	Serum phosphate levels (mg/dL) in Part B	Day 1, Day 14
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)
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: Amolyt Pharma

Publications and helpful links

General Publications

• Ovize M, Allas S, Culler MD, Milano S, Ouldrouis T, Sumeray M, van de Wetering de Rooij J, Mannstadt M. Phase 1 clinical trial of eneboparatide, a novel PTH receptor 1 agonist. Endocr Connect. 2025 Jun 19;14(6):e240464. doi: 10.1530/EC-24-0464. Print 2025 Jun 1.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2020
• Primary Completion (Actual): August 23, 2022
• Study Completion (Actual): August 23, 2022

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: February 1, 2022
• First Posted (Actual): February 14, 2022

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 4, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hypoparathyroidism; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: AZP-3601-CLI-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No