A Study Comparing Amorphous Calcium Carbonate (ACC) Versus Crystalline Calcium CCS) in Hypoparathyroidism Patients

NCT01815021 | Completed Phase 1

• 1 other identifier: AMCS 009
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective: Phase I Proof of concept: treatment with smaller doses of elemental calcium from ACC compared to CCS can maintain target serum calcium (corrected for albumin) values (7.0-10.0 mg/dL). Phase II To test the hypothesis that treatment with smaller doses of elemental calcium from ACC compared to CCS can maintain target serum calcium (corrected for albumin) values (7.0-10.0 mg/dL). Secondary objectives: Phase I

• ACC dose selection - to confirm the conversion factor of ACC from CCS
• To determine the effect of food on ACC absorption Phase II
• To test the hypothesis that treatment with smaller doses of elemental calcium from ACC compared to CCS will not cause an increase in hypercalciuria in patients with hypoparathyroidism
• To test the hypothesis that smaller doses of elemental calcium from ACC can reduce the side effects related with high calcium consumption. Amorphical has a strong basis to believe that the ACC product is better absorbed compared to the commercially available CCS products and therefore, can maintain desirable target albumin corrected calcium values in serum (CA) with smaller doses of elemental calcium from ACC. As results, the burden of taking high doses of calcium supplementation along with the side effects of the standard therapy (gastrointestinal discomfort and hypercalciuria) will be reduced. Testing serum CA and urine calcium values in subjects with hypoparathyroidism may provide a straightforward method to test this hypothesis. The study is designed to be conducted with extra precaution in order to avoid disturbing the fragile balance between CA levels in serum and calcium levels urine. The crossover design of phase II of the study allows a more accurate and reliable comparison of results attributable to the specific treatment within the same individual. In addition, the subjects will continue consuming all their routine medication throughout the trial. The subjects in the control arm will consume their routine calcium supplement doses thus, will be treated with a standard of care.

Conditions

Hypoparathyroidism

Outcome Measures

Primary Outcomes (1)

• Calcium (albumin-corrected) serum level - composite value based on multiple measurements

  The initial assessment of hypocal¬cemia is usually based on the measurement of serum total calcium corrected for albumin concentration. Normal CA values range from 8.5 to 10.2 mg/dL. In subjects with hypoparathyroidism, the desired target CA values are 7.0-10.0 mg/dL. The relationship between total serum calcium and albumin is defined by the following rule: the serum total calcium concentration falls by 0.8 mg/dL for every 1-g/dL fall in serum albumin concentration. This rule assumes that normal albumin equals 4.0 g/dL and normal calcium is 10.0 mg/dL. Calculation: Calcium (corrected, mmol/L) = Calcium (measured, mmol/L) + {(40 - albumin(g/L)) x 0.02}

  Blood tests will be performed for each subject in each CRC visit from day 0 and onward: Phase I: Day 0, 3, 7, 10, 14, 21, 28. Phase II: Day 0, 3, 7, 10, 14, 21, 35, 38, 42, 45, 49, 56, 70.

Secondary Outcomes (11)

• Urine calcium level - 24h urine collection

  Phase I: Termination of study (Day 28)

• Phosphorous serum level - composite value based on multiple measurements

  Blood tests will be performed for each subject in each CRC visit from day 0 and onward: Phase I: Day 0, 3, 7, 10, 14, 21, 28. Phase II: Day 0, 3, 7, 10, 14, 21, 35, 38, 42, 45, 49, 56, 70

• Urine calcium level - 24h urine collection

  Phase II: Day 35

• Urine calcium level - 24h urine collection

  Phase II: termination of study (Day 70)

• Assessment of symptoms and signs related with hypocalcemia - composite value based on multiple measurements

  Phase I: Day 7, 14, 21, 28 Phase II: Day 7, 14, 21, 35, 42, 49, 56, 70

Study Arms (2)

amorphous calcium carbonate

EXPERIMENTAL

50, 100 and 200 mg elemental calcium tablets, according to the doctor's decision

Dietary Supplement: amorphous calcium carbonate

crystalline calcium supplements

ACTIVE COMPARATOR

Tablets, according to the doctor's decision

Dietary Supplement: crystalline calcium supplements

Interventions

amorphous calcium carbonate DIETARY_SUPPLEMENT

Also known as: ACC

amorphous calcium carbonate

crystalline calcium supplements DIETARY_SUPPLEMENT

Also known as: CCS

crystalline calcium supplements

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary Hypoparathyroidism - low levels of intact PTH during hypocalcemia at diagnosis.
• Subjects receiving calcium and vitamin D supplementation at least 1 year prior to the beginning of the study.
• Subjects able to adhere to the visit schedule and protocol requirements and be available to complete the study.
• Subjects who provide written informed consent to participate in the study.
• Age: 18-80, inclusive.

You may not qualify if:

• Calcium (albumin corrected) serum values below 7.0 mg/dL or above 10.0 mg/dL
• Any known diseases affecting the absorption from the gastrointestinal tract:
• Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• Chronic diarrhea
• Subjects with neuropsychiatric disease.
• Subjects with impaired renal function (glomerular filtration rate, ≤40 mL/min)
• Subjects with other severe chronic disease requiring long-term therapy.
• Impaired liver function (Liver enzymes\> x3 upper limit of normal).
• Subjects with history or presence of kidney stones
• Recurrent urinary tract infections
• Subjects taking drugs which might affect calcium levels such as:
• Fusid
• Anticonvulsants
• Carbonic anhydrase
• Adrenocorticosteroids

Sponsors & Collaborators

• Amorphical Ltd.: lead

Study Sites (1)

Rambam Health Care Campus

Haifa, 31096, Israel

Location

MeSH Terms

Conditions

Hypoparathyroidism

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases

Study Officials

• Sophia Ish-Shalom, MD

  PRINCIPAL INVESTIGATOR

• Einat Dekel, DVM

  Amorphical Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2013
• First Posted: March 20, 2013
• Study Start: April 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: March 31, 2015

Record last verified: 2015-03

Locations

IL (1)