Clinical trial NCT05239221: AZP-3601 SAD and MAD Study in Healthy Subjects and Patients With Hypoparathyroidism
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Hypoparathyroidism
Lead sponsor: Amolyt Pharma
Sponsor class: INDUSTRY
First posted: 2022-02-14
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 2 weeks in Part A and Part B, and up to 3 months in Part C
Secondary outcomes:
measure: Observed Maximum Concentration (Cmax) - Part A
timeFrame: 24 hours
measure: Observed Maximum Concentration (Cmax) - Part B
timeFrame: Day 1, Day 14
measure: Observed Maximum Concentration (Cmax) - Part C
timeFrame: Day 1, Day 14, Day 28, Day 84
measure: Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A
timeFrame: 24 hours
measure: Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B
timeFrame: Day 1, Day 14
measure: Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C
timeFrame: Day 1, Day 14, Day 28, Day 84
measure: Calcium Corrected for Albumin - Part A
timeFrame: 24 hours
measure: Calcium Corrected for Albumin - Part B
timeFrame: 24 hours, Day 14
measure: Calcium Corrected for Albumin - Part C
timeFrame: Day 1, Day 14, Day 28 and Day 84
measure: Serum Phosphate - Part A
timeFrame: 24 hours
measure: Serum Phosphate - Part B
timeFrame: Day 1, Day 14
measure: Serum Phosphate - Part C
timeFrame: Day 1 (H0), Day 14 (H2), Day 28 (H2) and Day 84 (H2)
measure: Daily Dose of Oral Calcium and Active Vitamin D - Part C
timeFrame: Day 28 and Day 43
Other outcomes:
measure: Calcium Excretion Rate 24h- Part C
timeFrame: Day 1, Day 14, Day 28 and Day 84
Locations:
city: Budapest
country: Hungary
facility: Amolyt Pharma Investigational Site Hungary
city: Groningen
country: Netherlands
facility: PRA-EDS
Study officials:
References: