Chronic Hypoparathyroidism
Conditions
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.
Interventions
DRUGAZP-3601
Lyophilized powder of AZP-3601 to be reconstituted with water for injection before injection
DRUGPlacebo
Saline solution visually matching active medication
Sponsors
Amolyt Pharma
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part C is open label
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent Adverse Events (TEAEs) | Up to 2 weeks in Part A and Part B, and up to 3 months in Part C | Number of Treatment Emergent Adverse Events (TEAEs), as assessed by medDRA (v25). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Observed Maximum Concentration (Cmax) - Part A | 24 hours | Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part A |
| Observed Maximum Concentration (Cmax) - Part B | Day 1, Day 14 | Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part B |
| Observed Maximum Concentration (Cmax) - Part C | Day 1, Day 14, Day 28, Day 84 | Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part C. |
| Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A | 24 hours | Area under the plasma-drug concentration time curve (AUC) (pg\*h/mL) in Part A |
| Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 1, Day 14 | Area Under the Plasma-drug Concentration Time Curve (AUC) (pg\*h/mL) in Part B |
| Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C | Day 1, Day 14, Day 28, Day 84 | Area Under the Plasma-drug Concentration Time Curve (AUC) (pg\*h/mL) in Part C. |
| Calcium Corrected for Albumin - Part B | 24 hours, Day 14 | Levels of calcium corrected for albumin (mg/dL) in Part B |
| Calcium Corrected for Albumin - Part C | Day 1, Day 14, Day 28 and Day 84 | Levels of calcium corrected for albumin (mg/dL) in Part C. |
| Serum Phosphate - Part A | 24 hours | Serum phosphate levels (mg/dL) in Part A |
| Serum Phosphate - Part B | Day 1, Day 14 | Serum phosphate levels (mg/dL) in Part B |
| Serum Phosphate - Part C | Day 1 (H0), Day 14 (H2), Day 28 (H2) and Day 84 (H2) | Serum phosphate levels (mg/dL) in Part C. |
| Daily Dose of Oral Calcium and Active Vitamin D - Part C | Day 28 and Day 43 | Daily dose of oral calcium and active vitamin D for patients treated in Part C. |
| Calcium Corrected for Albumin - Part A | 24 hours | Levels of calcium corrected for albumin (mg/dL) in Part A |
Other
| Measure | Time frame | Description |
|---|---|---|
| Calcium Excretion Rate 24h- Part C | Day 1, Day 14, Day 28 and Day 84 | 24 hour calcium excretion rate (mg/24h) in Part C. |
Countries
Hungary, Netherlands
Participant flow
Pre-assignment details
A total of 132 subjects were enrolled in the study. Of those, 52 subjects were enrolled in Part A (Phase 1), 52 subjects were enrolled in Part B (Phase 1), and 28 subjects were enrolled in Part C (Phase 2a).
Participants by arm
| Arm | Count |
|---|---|
| Part A (Cohort A1, 5 ug Dose) Healthy volunteers were administered a single subcutaneous (SC) dose of 5ug of AZP-3601 on Day 1. | 3 |
| Part A (Cohort A2, 10 ug Dose) Healthy volunteers were administered a single subcutaneous (SC) dose of 10 ug of AZP-3601 on Day 1. | 6 |
| Part A (Cohort A3, 20 ug Dose) Healthy volunteers were administered a single subcutaneous (SC) dose of 20 ug of AZP-3601 on Day 1. | 6 |
| Part A (Cohort A4, 40 ug Dose) Healthy volunteers were administered a single subcutaneous (SC) dose of 40 ug of AZP-3601 on Day 1. | 6 |
| Part A (Cohort A5, 60 ug Dose) Healthy volunteers were administered a single subcutaneous (SC) dose of 60 ug of AZP-3601 on Day 1. | 6 |
| Part A (Cohort A6, 120 ug Dose) Healthy volunteers were administered a single subcutaneous (SC) dose of 120 ug of AZP-3601 on Day 1. | 6 |
| Part A (Cohort A7, 90 ug Dose) Healthy volunteers were administered a single subcutaneous (SC) dose of 90 ug of AZP-3601 on Day 1. | 6 |
| Part A (Placebo) Healthy volunteers were administered a single, subcutaneous dose of placebo on Day 1. | 13 |
| Part B (Cohort B1, 10 ug Doses) Healthy volunteers were administered a multiple subcutaneous (SC) doses of 10 ug of AZP-3601, once daily, from Day 1 to Day 14. | 8 |
| Part B (Cohort B2, 20 ug Doses) Healthy volunteers were administered a multiple subcutaneous (SC) doses of 20 ug of AZP-3601, once daily, from Day 1 to Day 14. | 8 |
| Part B (Cohort B3, 40 ug Doses) Healthy volunteers were administered a multiple subcutaneous (SC) doses of 40 ug of AZP-3601, once daily, from Day 1 to Day 14. | 10 |
| Part B (Cohort B4, 60 ug Doses) Healthy volunteers were administered a multiple subcutaneous (SC) doses of 60 ug of AZP-3601, once daily, from Day 1 to Day 14. | 8 |
| Part B (Cohort B5, 80 ug Doses) Healthy volunteers were administered a multiple subcutaneous (SC) doses of 80 ug of AZP-3601, once daily, from Day 1 to Day 14. | 8 |
| Part B (Placebo) Healthy volunteers were administered a multiple subcutaneous (SC) doses of placebo, once daily, from Day 1 to Day 14. | 10 |
| Part C (Cohort C1, Starting Dose of 20 ug/Day) Patients with hypoparathyroidism were treated with a once daily subcutaneous doses of AZP-3601 from Day 1 to Day 84. The starting dose was 20 ug/day, and up-titration of the dose was allowed from Day 14 onwards. | 12 |
| Part C (Cohort C2, Starting Dose of 10 ug/Day) Patients with hypoparathyroidism were treated with a once daily subcutaneous doses of AZP-3601 from Day 1 to Day 84. The starting dose was 10 ug/day, and up-titration of the dose was allowed from Day 14 onwards. | 16 |
| Total | 132 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A (Cohort A2, 10 ug Dose) | Part A (Cohort A3, 20 ug Dose) | Part A (Cohort A4, 40 ug Dose) | Part A (Cohort A5, 60 ug Dose) | Part A (Cohort A6, 120 ug Dose) | Part A (Cohort A7, 90 ug Dose) | Part A (Placebo) | Part B (Cohort B1, 10 ug Doses) | Part A (Cohort A1, 5 ug Dose) | Part B (Cohort B2, 20 ug Doses) | Part B (Cohort B3, 40 ug Doses) | Part B (Cohort B4, 60 ug Doses) | Part B (Cohort B5, 80 ug Doses) | Part B (Placebo) | Part C (Cohort C1, Starting Dose of 20 ug/Day) | Part C (Cohort C2, Starting Dose of 10 ug/Day) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.8 years | 23.7 years | 30.0 years | 26.3 years | 21.0 years | 35.3 years | 29.2 years | 38.3 years | 29.3 years | 42.9 years | 39.7 years | 30.1 years | 33.3 years | 32.0 years | 62.7 years | 54.0 years | 37.9 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 12 Participants | 8 Participants | 3 Participants | 8 Participants | 9 Participants | 7 Participants | 6 Participants | 7 Participants | 12 Participants | 15 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 10 Participants | 8 Participants | 3 Participants | 5 Participants | 10 Participants | 7 Participants | 3 Participants | 7 Participants | 12 Participants | 16 Participants | 112 Participants |
| Region of Enrollment France | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 6 participants | 6 participants |
| Region of Enrollment Hungary | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 9 participants | 6 participants | 15 participants |
| Region of Enrollment Netherlands | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 6 participants | 13 participants | 8 participants | 3 participants | 8 participants | 10 participants | 8 participants | 8 participants | 10 participants | 0 participants | 0 participants | 104 participants |
| Region of Enrollment Spain | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 3 participants | 4 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 9 Participants | 12 Participants | 25 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 13 Participants | 8 Participants | 3 Participants | 6 Participants | 9 Participants | 8 Participants | 8 Participants | 9 Participants | 3 Participants | 4 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 13 | 0 / 8 | 0 / 8 | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 10 | 0 / 12 | 0 / 16 |
| other Total, other adverse events | 2 / 3 | 3 / 6 | 5 / 6 | 1 / 6 | 3 / 6 | 6 / 6 | 6 / 6 | 8 / 13 | 6 / 8 | 7 / 8 | 10 / 10 | 8 / 8 | 7 / 8 | 9 / 10 | 7 / 12 | 12 / 16 |
| serious Total, serious adverse events | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 13 | 0 / 8 | 0 / 8 | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 10 | 0 / 12 | 0 / 16 |
Outcome results
Primary
Treatment Emergent Adverse Events (TEAEs)
Number of Treatment Emergent Adverse Events (TEAEs), as assessed by medDRA (v25).
Time frame: Up to 2 weeks in Part A and Part B, and up to 3 months in Part C
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| Part A (Cohort A2, 10 ug Dose) | Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Part A (Cohort A3, 20 ug Dose) | Treatment Emergent Adverse Events (TEAEs) | 5 Participants |
| Part A (Cohort A4, 40 ug Dose) | Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| Part A (Cohort A5, 60 ug Dose) | Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Part A (Cohort A6, 120 ug Dose) | Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Part A (Cohort A7, 90 ug Dose) | Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Part A (Placebo) | Treatment Emergent Adverse Events (TEAEs) | 8 Participants |
| Part B (Cohort B1, 10 ug Doses) | Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Part B (Cohort B2, 20 ug Doses) | Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| Part B (Cohort B3, 40 ug Doses) | Treatment Emergent Adverse Events (TEAEs) | 10 Participants |
| Part B (Cohort B4, 60 ug Doses) | Treatment Emergent Adverse Events (TEAEs) | 8 Participants |
| Part B (Cohort B5, 80 ug Doses) | Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| Part B (Placebo) | Treatment Emergent Adverse Events (TEAEs) | 9 Participants |
| Part C (Cohort C1, Starting Dose of 20 ug/Day) | Treatment Emergent Adverse Events (TEAEs) | 7 Participants |
| Part C (Cohort C2, Starting Dose of 10 ug/Day) | Treatment Emergent Adverse Events (TEAEs) | 12 Participants |
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
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A | 0.399 pg*h/mL | Standard Deviation 0.032 |
| Part A (Cohort A2, 10 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A | 5.20 pg*h/mL | Standard Deviation 3.38 |
| Part A (Cohort A3, 20 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A | 9.55 pg*h/mL | Standard Deviation 4.12 |
| Part A (Cohort A4, 40 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A | 10.4 pg*h/mL | Standard Deviation 13.4 |
| Part A (Cohort A5, 60 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A | 16.8 pg*h/mL | Standard Deviation 14.7 |
| Part A (Cohort A6, 120 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A | 26.1 pg*h/mL | Standard Deviation 16.4 |
| Part A (Cohort A7, 90 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part A | 31.7 pg*h/mL | Standard Deviation 12.5 |
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
Time frame: Day 1, Day 14
Population: Data not collected for a few subjects (missing data or site error).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 1 | 3.26 pg*h/mL | Standard Deviation 3.2 |
| Part A (Cohort A1, 5 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 14 | 2.02 pg*h/mL | Standard Deviation 2.41 |
| Part A (Cohort A2, 10 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 1 | 7.69 pg*h/mL | Standard Deviation 5.52 |
| Part A (Cohort A2, 10 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 14 | 4.63 pg*h/mL | Standard Deviation 3.29 |
| Part A (Cohort A3, 20 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 1 | 15.8 pg*h/mL | Standard Deviation 11.5 |
| Part A (Cohort A3, 20 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 14 | 12.5 pg*h/mL | Standard Deviation 4.75 |
| Part A (Cohort A4, 40 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 14 | 58.8 pg*h/mL | Standard Deviation 30.3 |
| Part A (Cohort A4, 40 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 1 | 43.3 pg*h/mL | Standard Deviation 18.1 |
| Part A (Cohort A5, 60 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 1 | 64.2 pg*h/mL | Standard Deviation 56.1 |
| Part A (Cohort A5, 60 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part B | Day 14 | 51.9 pg*h/mL | Standard Deviation 51.6 |
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.
Time frame: Day 1, Day 14, Day 28, Day 84
Population: One (1) subject dropped out in Cohort 2 prior to the extension phase and one (1) subject from Cohort 2 did not participate in the extension phase (data on Day 84). In addition, data not collected for a few subjects (missing data or site error). Pharmacokinetic (PK) data was not collected in Cohort 1 on Day 84 per the protocol at the time. The protocol was updated following completion of Cohort 1 to collect PK information in Cohort 2 on Day 84.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C | Day 28 | 12.7 pg*h/mL | Standard Deviation 7.58 |
| Part A (Cohort A1, 5 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C | Day 14 | 16.1 pg*h/mL | Standard Deviation 14 |
| Part A (Cohort A1, 5 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C | Day 1 | 11.9 pg*h/mL | Standard Deviation 9.53 |
| Part A (Cohort A2, 10 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C | Day 84 | 116 pg*h/mL | Standard Deviation 111 |
| Part A (Cohort A2, 10 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C | Day 14 | 3.99 pg*h/mL | Standard Deviation 4.22 |
| Part A (Cohort A2, 10 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C | Day 1 | 4.90 pg*h/mL | Standard Deviation 4.87 |
| Part A (Cohort A2, 10 ug Dose) | Area Under the Plasma-drug Concentration Time Curve (AUC) - Part C | Day 28 | 11.8 pg*h/mL | Standard Deviation 11.1 |
Secondary
Calcium Corrected for Albumin - Part A
Levels of calcium corrected for albumin (mg/dL) in Part A
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Calcium Corrected for Albumin - Part A | 9.700 mg/dL | Standard Deviation 0.08 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Corrected for Albumin - Part A | 9.375 mg/dL | Standard Deviation 0.6215 |
| Part A (Cohort A3, 20 ug Dose) | Calcium Corrected for Albumin - Part A | 9.688 mg/dL | Standard Deviation 0.3448 |
| Part A (Cohort A4, 40 ug Dose) | Calcium Corrected for Albumin - Part A | 9.782 mg/dL | Standard Deviation 0.4303 |
| Part A (Cohort A5, 60 ug Dose) | Calcium Corrected for Albumin - Part A | 10.065 mg/dL | Standard Deviation 0.2934 |
| Part A (Cohort A6, 120 ug Dose) | Calcium Corrected for Albumin - Part A | 10.293 mg/dL | Standard Deviation 0.5258 |
| Part A (Cohort A7, 90 ug Dose) | Calcium Corrected for Albumin - Part A | 10.195 mg/dL | Standard Deviation 0.2601 |
| Part A (Placebo) | Calcium Corrected for Albumin - Part A | 9.634 mg/dL | Standard Deviation 0.303 |
Secondary
Calcium Corrected for Albumin - Part B
Levels of calcium corrected for albumin (mg/dL) in Part B
Time frame: 24 hours, Day 14
Population: One (1) subject in Cohort B4 discontinued from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Calcium Corrected for Albumin - Part B | 24 hours | 9.818 mg/dL | Standard Deviation 0.3283 |
| Part A (Cohort A1, 5 ug Dose) | Calcium Corrected for Albumin - Part B | Day 14 | 9.586 mg/dL | Standard Deviation 0.3173 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Corrected for Albumin - Part B | 24 hours | 9.661 mg/dL | Standard Deviation 0.3492 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Corrected for Albumin - Part B | Day 14 | 9.650 mg/dL | Standard Deviation 0.2081 |
| Part A (Cohort A3, 20 ug Dose) | Calcium Corrected for Albumin - Part B | 24 hours | 10.121 mg/dL | Standard Deviation 0.432 |
| Part A (Cohort A3, 20 ug Dose) | Calcium Corrected for Albumin - Part B | Day 14 | 10.055 mg/dL | Standard Deviation 0.5916 |
| Part A (Cohort A4, 40 ug Dose) | Calcium Corrected for Albumin - Part B | 24 hours | 10.01 mg/dL | Standard Deviation 0.3 |
| Part A (Cohort A4, 40 ug Dose) | Calcium Corrected for Albumin - Part B | Day 14 | 10.06 mg/dL | Standard Deviation 0.59 |
| Part A (Cohort A5, 60 ug Dose) | Calcium Corrected for Albumin - Part B | 24 hours | 10.01 mg/dL | Standard Deviation 0.41 |
| Part A (Cohort A5, 60 ug Dose) | Calcium Corrected for Albumin - Part B | Day 14 | 10.94 mg/dL | Standard Deviation 0.97 |
| Part A (Cohort A6, 120 ug Dose) | Calcium Corrected for Albumin - Part B | 24 hours | 9.68 mg/dL | Standard Deviation 0.21 |
| Part A (Cohort A6, 120 ug Dose) | Calcium Corrected for Albumin - Part B | Day 14 | 9.79 mg/dL | Standard Deviation 0.24 |
Secondary
Calcium Corrected for Albumin - Part C
Levels of calcium corrected for albumin (mg/dL) in Part C.
Time frame: Day 1, Day 14, Day 28 and Day 84
Population: One (1) subject dropped out in Cohort 2 prior to the extension phase. In addition to this subject, two (2) subjects from Cohort 1 and one (1) subject from Cohort 2 did not participate in the extension phase (data on Day 84). In addition, data not collected for a few subjects (missing data or site error).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Calcium Corrected for Albumin - Part C | Day 1 (hour 0) | 8.44 mg/dL | Standard Deviation 0.42 |
| Part A (Cohort A1, 5 ug Dose) | Calcium Corrected for Albumin - Part C | Day 14 | 8.48 mg/dL | Standard Deviation 0.537 |
| Part A (Cohort A1, 5 ug Dose) | Calcium Corrected for Albumin - Part C | Day 28 | 8.64 mg/dL | Standard Deviation 0.491 |
| Part A (Cohort A1, 5 ug Dose) | Calcium Corrected for Albumin - Part C | Day 84 | 7.95 mg/dL | Standard Deviation 0.817 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Corrected for Albumin - Part C | Day 84 | 8.73 mg/dL | Standard Deviation 0.878 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Corrected for Albumin - Part C | Day 1 (hour 0) | 8.61 mg/dL | Standard Deviation 0.552 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Corrected for Albumin - Part C | Day 28 | 8.537 mg/dL | Standard Deviation 0.697 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Corrected for Albumin - Part C | Day 14 | 8.38 mg/dL | Standard Deviation 0.726 |
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.
Time frame: Day 28 and Day 43
Population: * One (1) subject dropped out in Cohort 2 prior to the extension phase. In addition to this subject, two (2) subjects from Cohort 1 and one (1) subject from Cohort 2 did not participate in the extension phase (data on Day 84). For this reason, data was collected in ten (10) subjects in Cohort 1 and fourteen (14) subjects in Cohort 2 on Day 84.~* On Day 84, one (1) patient in Cohort 1 was mistakenly given vitamin D. This patient is included in the nine (9) patients taking no vit D on Day 84.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Daily Dose of Oral Calcium and Active Vitamin D - Part C | Number of patients taking =< 500 mg/day of calcium on Day 28 | 9 Participants |
| Part A (Cohort A1, 5 ug Dose) | Daily Dose of Oral Calcium and Active Vitamin D - Part C | Number of patients taking =< 500 mg/day of calcium on Day 84 | 8 Participants |
| Part A (Cohort A1, 5 ug Dose) | Daily Dose of Oral Calcium and Active Vitamin D - Part C | Number of patients taking no vitamin D on Day 28 | 10 Participants |
| Part A (Cohort A1, 5 ug Dose) | Daily Dose of Oral Calcium and Active Vitamin D - Part C | Number of patients taking no vitamin D on Day 84 | 9 Participants |
| Part A (Cohort A2, 10 ug Dose) | Daily Dose of Oral Calcium and Active Vitamin D - Part C | Number of patients taking no vitamin D on Day 84 | 13 Participants |
| Part A (Cohort A2, 10 ug Dose) | Daily Dose of Oral Calcium and Active Vitamin D - Part C | Number of patients taking =< 500 mg/day of calcium on Day 28 | 12 Participants |
| Part A (Cohort A2, 10 ug Dose) | Daily Dose of Oral Calcium and Active Vitamin D - Part C | Number of patients taking no vitamin D on Day 28 | 12 Participants |
| Part A (Cohort A2, 10 ug Dose) | Daily Dose of Oral Calcium and Active Vitamin D - Part C | Number of patients taking =< 500 mg/day of calcium on Day 84 | 13 Participants |
Secondary
Observed Maximum Concentration (Cmax) - Part A
Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part A
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Observed Maximum Concentration (Cmax) - Part A | 6.82 pg/mL | Standard Deviation 2.19 |
| Part A (Cohort A2, 10 ug Dose) | Observed Maximum Concentration (Cmax) - Part A | 11.4 pg/mL | Standard Deviation 4.32 |
| Part A (Cohort A3, 20 ug Dose) | Observed Maximum Concentration (Cmax) - Part A | 24.1 pg/mL | Standard Deviation 8.18 |
| Part A (Cohort A4, 40 ug Dose) | Observed Maximum Concentration (Cmax) - Part A | 26.3 pg/mL | Standard Deviation 4.79 |
| Part A (Cohort A5, 60 ug Dose) | Observed Maximum Concentration (Cmax) - Part A | 28.5 pg/mL | Standard Deviation 10.8 |
| Part A (Cohort A6, 120 ug Dose) | Observed Maximum Concentration (Cmax) - Part A | 57.4 pg/mL | Standard Deviation 28.7 |
| Part A (Cohort A7, 90 ug Dose) | Observed Maximum Concentration (Cmax) - Part A | 37.5 pg/mL | Standard Deviation 11.6 |
Secondary
Observed Maximum Concentration (Cmax) - Part B
Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part B
Time frame: Day 1, Day 14
Population: Data not collected for a few subjects (missing data or site error)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 1 | 20.6 pg/mL | Standard Deviation 3.43 |
| Part A (Cohort A1, 5 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 14 | 18.4 pg/mL | Standard Deviation 5.37 |
| Part A (Cohort A2, 10 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 1 | 19.6 pg/mL | Standard Deviation 5.68 |
| Part A (Cohort A2, 10 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 14 | 18.3 pg/mL | Standard Deviation 6.78 |
| Part A (Cohort A3, 20 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 1 | 23.8 pg/mL | Standard Deviation 8.97 |
| Part A (Cohort A3, 20 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 14 | 23.6 pg/mL | Standard Deviation 5.5 |
| Part A (Cohort A4, 40 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 14 | 44.9 pg/mL | Standard Deviation 17.9 |
| Part A (Cohort A4, 40 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 1 | 42.9 pg/mL | Standard Deviation 30.3 |
| Part A (Cohort A5, 60 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 1 | 124 pg/mL | Standard Deviation 105 |
| Part A (Cohort A5, 60 ug Dose) | Observed Maximum Concentration (Cmax) - Part B | Day 14 | 63.5 pg/mL | Standard Deviation 28.3 |
Secondary
Observed Maximum Concentration (Cmax) - Part C
Observed maximum concentration (Cmax) of AZP-3601 (pg/mL) in Part C.
Time frame: Day 1, Day 14, Day 28, Day 84
Population: One (1) subject dropped out in Cohort 2 prior to the extension phase and one (1) subject from Cohort 2 did not participate in the extension phase (data on Day 84). In addition, data not collected for a few subjects (missing data or site error). PK data was not collected in Cohort 1 on Day 84 per the protocol at the time. The protocol was updated following completion of Cohort 1 to collect PK information in Cohort 2 on Day 84.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Observed Maximum Concentration (Cmax) - Part C | Day 28 | 18.4 pg/mL | Standard Deviation 7.42 |
| Part A (Cohort A1, 5 ug Dose) | Observed Maximum Concentration (Cmax) - Part C | Day 14 | 22.3 pg/mL | Standard Deviation 11.7 |
| Part A (Cohort A1, 5 ug Dose) | Observed Maximum Concentration (Cmax) - Part C | Day 1 | 21.3 pg/mL | Standard Deviation 9.2 |
| Part A (Cohort A2, 10 ug Dose) | Observed Maximum Concentration (Cmax) - Part C | Day 84 | 89.9 pg/mL | Standard Deviation 63.9 |
| Part A (Cohort A2, 10 ug Dose) | Observed Maximum Concentration (Cmax) - Part C | Day 14 | 10.4 pg/mL | Standard Deviation 7.73 |
| Part A (Cohort A2, 10 ug Dose) | Observed Maximum Concentration (Cmax) - Part C | Day 1 | 11.9 pg/mL | Standard Deviation 7.82 |
| Part A (Cohort A2, 10 ug Dose) | Observed Maximum Concentration (Cmax) - Part C | Day 28 | 21.5 pg/mL | Standard Deviation 17.9 |
Secondary
Serum Phosphate - Part A
Serum phosphate levels (mg/dL) in Part A
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Serum Phosphate - Part A | 3.353 mg/dL | Standard Deviation 0.6646 |
| Part A (Cohort A2, 10 ug Dose) | Serum Phosphate - Part A | 2.882 mg/dL | Standard Deviation 0.3884 |
| Part A (Cohort A3, 20 ug Dose) | Serum Phosphate - Part A | 3.840 mg/dL | Standard Deviation 0.5135 |
| Part A (Cohort A4, 40 ug Dose) | Serum Phosphate - Part A | 3.287 mg/dL | Standard Deviation 0.5021 |
| Part A (Cohort A5, 60 ug Dose) | Serum Phosphate - Part A | 3.908 mg/dL | Standard Deviation 0.5051 |
| Part A (Cohort A6, 120 ug Dose) | Serum Phosphate - Part A | 3.673 mg/dL | Standard Deviation 0.4975 |
| Part A (Cohort A7, 90 ug Dose) | Serum Phosphate - Part A | 3.417 mg/dL | Standard Deviation 0.4133 |
| Part A (Placebo) | Serum Phosphate - Part A | 3.641 mg/dL | Standard Deviation 0.3637 |
Secondary
Serum Phosphate - Part B
Serum phosphate levels (mg/dL) in Part B
Time frame: Day 1, Day 14
Population: One (1) subject in Cohort B4 discontinued from the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Serum Phosphate - Part B | Day 1 | 3.616 mg/dL | Standard Deviation 0.1919 |
| Part A (Cohort A1, 5 ug Dose) | Serum Phosphate - Part B | Day 14 | 3.601 mg/dL | Standard Deviation 0.2299 |
| Part A (Cohort A2, 10 ug Dose) | Serum Phosphate - Part B | Day 14 | 3.850 mg/dL | Standard Deviation 0.3397 |
| Part A (Cohort A2, 10 ug Dose) | Serum Phosphate - Part B | Day 1 | 3.751 mg/dL | Standard Deviation 0.3229 |
| Part A (Cohort A3, 20 ug Dose) | Serum Phosphate - Part B | Day 1 | 3.824 mg/dL | Standard Deviation 0.5421 |
| Part A (Cohort A3, 20 ug Dose) | Serum Phosphate - Part B | Day 14 | 3.603 mg/dL | Standard Deviation 0.4738 |
| Part A (Cohort A4, 40 ug Dose) | Serum Phosphate - Part B | Day 1 | 3.518 mg/dL | Standard Deviation 0.3332 |
| Part A (Cohort A4, 40 ug Dose) | Serum Phosphate - Part B | Day 14 | 3.727 mg/dL | Standard Deviation 0.397 |
| Part A (Cohort A5, 60 ug Dose) | Serum Phosphate - Part B | Day 1 | 3.398 mg/dL | Standard Deviation 0.3965 |
| Part A (Cohort A5, 60 ug Dose) | Serum Phosphate - Part B | Day 14 | 3.553 mg/dL | Standard Deviation 0.6037 |
| Part A (Cohort A6, 120 ug Dose) | Serum Phosphate - Part B | Day 14 | 3.74 mg/dL | Standard Deviation 0.4 |
| Part A (Cohort A6, 120 ug Dose) | Serum Phosphate - Part B | Day 1 | 3.65 mg/dL | Standard Deviation 0.58 |
Secondary
Serum Phosphate - Part C
Serum phosphate levels (mg/dL) in Part C.
Time frame: Day 1 (H0), Day 14 (H2), Day 28 (H2) and Day 84 (H2)
Population: One (1) subject dropped out in Cohort 2 prior to the extension phase. In addition to this subject, two (2) subjects from Cohort 1 and one (1) subject from Cohort 2 did not participate in the extension phase (data on Day 84). For this reason, data was collected in ten (10) subjects in Cohort 1 and fourteen (14) subjects in Cohort 2 on Day 84. In addition, data not collected for a few subjects (missing data or site error).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Serum Phosphate - Part C | Day 1 | 4.12 mg/dL | Standard Deviation 0.798 |
| Part A (Cohort A1, 5 ug Dose) | Serum Phosphate - Part C | Day 14 | 3.43 mg/dL | Standard Deviation 0.742 |
| Part A (Cohort A1, 5 ug Dose) | Serum Phosphate - Part C | Day 28 | 3.50 mg/dL | Standard Deviation 0.843 |
| Part A (Cohort A1, 5 ug Dose) | Serum Phosphate - Part C | Day 84 | 3.60 mg/dL | Standard Deviation 0.589 |
| Part A (Cohort A2, 10 ug Dose) | Serum Phosphate - Part C | Day 84 | 3.80 mg/dL | Standard Deviation 6.83 |
| Part A (Cohort A2, 10 ug Dose) | Serum Phosphate - Part C | Day 1 | 4.53 mg/dL | Standard Deviation 0.78 |
| Part A (Cohort A2, 10 ug Dose) | Serum Phosphate - Part C | Day 28 | 3.82 mg/dL | Standard Deviation 0.868 |
| Part A (Cohort A2, 10 ug Dose) | Serum Phosphate - Part C | Day 14 | 3.95 mg/dL | Standard Deviation 0.849 |
Other Pre-specified
Calcium Excretion Rate 24h- Part C
24 hour calcium excretion rate (mg/24h) in Part C.
Time frame: Day 1, Day 14, Day 28 and Day 84
Population: One (1) subject dropped out in Cohort 2 prior to the extension phase. In addition to this subject, two (2) subjects from Cohort 1 and one (1) subject from Cohort 2 did not participate in the extension phase (data on Day 84). For this reason, data was collected in ten (10) subjects in Cohort 1 and fourteen (14) subjects in Cohort 2 on Day 84. In addition, data not collected for a few subjects (missing data or site error).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A (Cohort A1, 5 ug Dose) | Calcium Excretion Rate 24h- Part C | Day 1 | 328.72 mg/24h | Standard Deviation 130.95 |
| Part A (Cohort A1, 5 ug Dose) | Calcium Excretion Rate 24h- Part C | Day 14 | 224.83 mg/24h | Standard Deviation 108.57 |
| Part A (Cohort A1, 5 ug Dose) | Calcium Excretion Rate 24h- Part C | Day 28 | 155.06 mg/24h | Standard Deviation 61.705 |
| Part A (Cohort A1, 5 ug Dose) | Calcium Excretion Rate 24h- Part C | Day 84 | 115.70 mg/24h | Standard Deviation 37.929 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Excretion Rate 24h- Part C | Day 84 | 145.15 mg/24h | Standard Deviation 113.563 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Excretion Rate 24h- Part C | Day 1 | 330.73 mg/24h | Standard Deviation 189.154 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Excretion Rate 24h- Part C | Day 28 | 166.43 mg/24h | Standard Deviation 96.637 |
| Part A (Cohort A2, 10 ug Dose) | Calcium Excretion Rate 24h- Part C | Day 14 | 188.41 mg/24h | Standard Deviation 100.054 |