A Study Comparing Amorphous Calcium Carbonate (ACC) Versus Crystalline Calcium CCS) in Hypoparathyroidism Patients (AMCS009)

• ClinicalTrials.gov Identifier: NCT01815021
• Recruitment Status: Completed
• First Posted: March 20, 2013
• Last Update Posted: March 31, 2015
• Sponsor: Amorphical Ltd.
• Information provided by (Responsible Party): Amorphical Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypoparathyroidism	Dietary Supplement: amorphous calcium carbonate; Dietary Supplement: crystalline calcium supplements	Phase 1; Phase 2

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Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Two Phase, Adaptive Then Crossover Open-label, Study Comparing Amorphous Calcium Carbonate (ACC) Supplement Versus Commercially Available Crystalline Calcium Supplements (CCS) in the Management of Primary Hypoparathyroidism.
• Study Start Date: April 2013
• Actual Primary Completion Date: June 2014
• Actual Study Completion Date: June 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: amorphous calcium carbonate; 50, 100 and 200 mg elemental calcium tablets, according to the doctor's decision	Dietary Supplement: amorphous calcium carbonate; Other Name: ACC
Active Comparator: crystalline calcium supplements; Tablets, according to the doctor's decision	Dietary Supplement: crystalline calcium supplements; Other Name: CCS

Outcome Measures

Primary Outcome Measures :

1. Calcium (albumin-corrected) serum level - composite value based on multiple measurements [ Time Frame: 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. ]

   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}

Secondary Outcome Measures :

1. Urine calcium level - 24h urine collection [ Time Frame: Phase I: Termination of study (Day 28) ]

   For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

   Urine calcium level > 300 mg/24 hours or > 4 mg/kg of weight/24 hours is considered as hypercalciuria.

2. Phosphorous serum level - composite value based on multiple measurements [ Time Frame: 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 ]
   The serum phosphorus test measures the amount of phosphate in the blood. Normal values range from 2.4 - 4.1 mg/dL
3. Urine calcium level - 24h urine collection [ Time Frame: Phase II: Day 35 ]

   For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

   Urine calcium level > 300 mg/24 hours or > 4 mg/kg of weight/24 hours is considered as hypercalciuria.

4. Urine calcium level - 24h urine collection [ Time Frame: Phase II: termination of study (Day 70) ]

   For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

   Urine calcium level > 300 mg/24 hours or > 4 mg/kg of weight/24 hours is considered as hypercalciuria.

5. Assessment of symptoms and signs related with hypocalcemia - composite value based on multiple measurements [ Time Frame: Phase I: Day 7, 14, 21, 28 Phase II: Day 7, 14, 21, 35, 42, 49, 56, 70 ]
   At each visit to the CRC, subjects will be asked to answer questions for the presence of symptoms and signs related with hypocalcemia (tetany, facial grimacing, paresthesias, muscle aches, arrhythmia, depression).
6. Urine creatinine level - 24h urine collection [ Time Frame: Phase I: Termination of study (Day 28) ]

   For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

   A creatinine clearance test is done on a sample of urine collected over 24 hours. It is used to determine glomerular filtration rate, which helps to measure how well the kidney functions. The normal adult urine calcium/creatinine ratio is <220 mg/g

7. Urine creatinine level - 24h urine collection [ Time Frame: Phase II: Day 35 ]

   For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

   A creatinine clearance test is done on a sample of urine collected over 24 hours. It is used to determine glomerular filtration rate, which helps to measure how well the kidney functions. The normal adult urine calcium/creatinine ratio is <220 mg/g

8. Urine creatinine level - 24h urine collection [ Time Frame: Phase II: termination of study (Day 70) ]

   For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

   A creatinine clearance test is done on a sample of urine collected over 24 hours. It is used to determine glomerular filtration rate, which helps to measure how well the kidney functions. The normal adult urine calcium/creatinine ratio is <220 mg/g

9. Urine phosphorus level - 24h urine collection [ Time Frame: Phase I: Termination of study (Day 28) ]

   The phosphate urine test measures the amount of phosphate in a sample of urine collected over 24 hours (24-hour urine test). Phosphate is a charged ion that contains the mineral phosphorus.

   Results of a test to measure phosphate in urine are seldom useful on their own. They should always be interpreted along with the results of other tests. Calcium and phosphate levels are often measured at the same time.

10. Urine phosphorus level - 24h urine collection [ Time Frame: Phase II: Day 35 ]

    The phosphate urine test measures the amount of phosphate in a sample of urine collected over 24 hours (24-hour urine test). Phosphate is a charged ion that contains the mineral phosphorus.

    Results of a test to measure phosphate in urine are seldom useful on their own. They should always be interpreted along with the results of other tests. Calcium and phosphate levels are often measured at the same time.

11. Urine phosphorus level - 24h urine collection [ Time Frame: Phase II: termination of study (Day 70) ]

    The phosphate urine test measures the amount of phosphate in a sample of urine collected over 24 hours (24-hour urine test). Phosphate is a charged ion that contains the mineral phosphorus.

    Results of a test to measure phosphate in urine are seldom useful on their own. They should always be interpreted along with the results of other tests. Calcium and phosphate levels are often measured at the same time.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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
• Subjects who are non-cooperative or unwilling to sign consent form.
• Pregnant or breast-feeding women.

Contacts and Locations

Locations

Israel

Rambam Health Care Campus

Haifa, Israel, 31096

Sponsors and Collaborators

Amorphical Ltd.

Investigators

• Principal Investigator: Sophia Ish-Shalom, MD
• Study Director: Einat Dekel, DVM; Amorphical Ltd.

More Information

• Responsible Party: Amorphical Ltd.
• ClinicalTrials.gov Identifier: NCT01815021 History of Changes
• Other Study ID Numbers: AMCS 009
• First Posted: March 20, 2013
• Last Update Posted: March 31, 2015
• Last Verified: March 2015

Additional relevant MeSH terms:

Calcium, Dietary; Calcium Carbonate; Calcium; Calcium-Regulating Hormones and Agents; Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Physiological Effects of Drugs; Bone Density Conservation Agents; Antacids; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents