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

• ClinicalTrials.gov Identifier: NCT05239221
• Recruitment Status: Completed
• First Posted: February 14, 2022
• Last Update Posted: September 26, 2022
• Sponsor: Amolyt Pharma
• Information provided by (Responsible Party): Amolyt Pharma

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Chronic Hypoparathyroidism	Drug: AZP-3601; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Part C is open label
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 7, 2020
• Actual Primary Completion Date: August 23, 2022
• Actual Study Completion Date: August 23, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Treatment Emergent Adverse Events (TEAEs) [ Time Frame: up to 2 weeks (Parts A and B), up to 3 months (Part C) ]
   Number of TEAEs as assessed by medDRA

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Urinary Calcium levels [ Time Frame: up to 2 weeks (Parts A and B), up to 3 months (Part C) ]
   Levels of urinary calcium

Eligibility Criteria

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

Criteria

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:

  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.

Contacts and Locations

Locations

Hungary

Amolyt Pharma Investigational Site Hungary

Budapest, Hungary

Netherlands

PRA-EDS

Groningen, Netherlands, 9728

Sponsors and Collaborators

Amolyt Pharma

More Information

• Responsible Party: Amolyt Pharma
• ClinicalTrials.gov Identifier: NCT05239221
• Other Study ID Numbers: AZP-3601-CLI-001
• First Posted: February 14, 2022
• Last Update Posted: September 26, 2022
• Last Verified: September 2022

• 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

Additional relevant MeSH terms:

Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases