Recombinant Human rhPTH(1-34) VS Association Alfacalcidol/Hydrochlorothiazide in Severe Primary Hypoparathyroidism

• Register: ClinicalTrials.gov
• Last refreshed on: 5 July 2021
• Main ID: NCT02824718
• Date of registration: 01/07/2016
• Prospective Registration: Yes
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: Recombinant Human rhPTH(1-34) VS Association Alfacalcidol/Hydrochlorothiazide in Severe Primary Hypoparathyroidism ACTICAS
• Scientific title: A Randomized Crossover TrIal to Compare Recombinant Human rhPTH(1-34) to the ASsociation Alfacalcidol/Hydrochlorothiazide in the Treatment of Severe Primary Hypoparathyroidism
• Date of first enrolment: June 6, 2017
• Target sample size: 16
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02824718
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Agnes Linglart, MD, PhD
• Affiliation: Assistance Publique - Hôpitaux de Paris

• Name: Anne Blanchard, MD, PhD
• Affiliation: Assistance Publique - Hôpitaux de Paris

Key inclusion & exclusion criteria

Inclusion criteria :

- Patients aged from 18 to 80 years, of both sexes

- Patient with primary hypoparathyroidism related to a genetically proven ADH OR primary
hypoparathyroidism related to other cause but complicated by hypercalciuria under
treatment

- Affiliated to a French health insurance system, and who have consented to the study.

Exclusion criteria :

- Pregnant and breastfeeding women;

- Women of childbearing age without contraception;

- For men aged from 18 to 20 years, presence of cartilage of growth on X-ray of left
knee;

- Anuria;

- Kidney failure with plasmatic creatinine >125 mmol/l and urea >10 mmol/l;

- Long QT interval : QTc > 450 ms (men) or 470 ms (women);

- Hepatic failure;

- Metabolic bone diseases (Paget's disease of bone) other than primary osteoporosis or
glucocorticoid-induced osteoporosis;

- Association to other potassium sparing diuretics;

- Hypokalemia (<3.5 mmol/l) without diuretic therapy;

- Hyperkalemia (>5.5 mmol/l);

- Hyponatremia (<135 mmol/l) without diuretic therapy;

- Hypercalcemia (>2.6 mmol/l);

- Severe hypomagnesemia (= 0.5 mmol/l);

- Vitamin D deficiency (25OH vit D < 20 ng/mL);

- Unexplained increase in alkaline phosphatase (>2N);

- Intolerance to sulfamide;

- Intolerance to amiloride or other component of the drug;

- Hypersensitivity to any active substance or excipient of one of the experimental
drugs;

- Gluten intolerance;

- Bone break history within the three previous months;

- History of radiotherapy of the skeleton;

- History of bone cancer or metastasis.

- Personnal or familial (first degree relatives) of skin cancer



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Autosomal Dominant Hypocalcemia OR Primary Hypoparathyroidism Related to Other Cause But Complicated by Hypercalciuria Under Treatment

Intervention(s)

Drug: Alfacalcidol

Drug: Potassium sparing diuretic

Drug: Teriparatide

Drug: Thiazide

Primary Outcome(s)

Plasma calcium concentration [Time Frame: two months of treatment]

Secondary Outcome(s)

Blood pressure [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Number of episodes of cramps [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Serum 25 OH vitamin D level [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Serum magnesium level [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Serum potassium level [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Serum renin level [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Calcium/citrate ratio measured on spot urines [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Crystalluria [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

24h-urinary magnesium excretion [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Ambulatory calcium concentration [Time Frame: days 7 an 28 of treatment by rhPTH(1-34) and association alfacalcidol/hydrochlorothiazide and at day 14 of non-treatment periods (run in, wash out, run out).]

24h-urinary potassium excretion [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Calcium/creatinine ratios measured on spot urines [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

24h-urinary aldosterone excretion [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Serum sodium level [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Estimated GFR using MDRD formula [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Serum 1,25(OH)2 vitamin D level [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Calciuria [Time Frame: Inclusion, weeks 4 (end of the run-in period), 7-8 (end of the first treatment period), 11-12 (end of the wash-out period), 18-20 (end of the second treatment period), 202 (end of the wash-out period)]

Alkaline phosphatase level [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Number of episodes of paresthesia [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Serum aldosterone level [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

SF36 self-administered questionnaire [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Number of episodes of tetany [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Plasma calcium x phosphate product [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

24h-urinary sodium excretion [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Number of episodes of seizure [Time Frame: Inclusion, days 28 (end of the run-in period), 80 (end of the first treatment period), 108 (end of the wash-out period), 160 (end of the second treatment period), 202 (end of the wash-out period)]

Secondary ID(s)

2016-000500-29

P150911

PHRC-15-549

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Ministry of Health, France