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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Man

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 seru

Detailed Summary:

Eligible subjects will be treated as follows:

Phase I Ten (10) subjects previously diagnosed and chronically treated for primary hypoparathyroidism will be enrolled. The daily CCS intake will be gradually replaced by reduced amount of elemental calcium from ACC. Five (5) subjects will consume the ACC before having a meal and the other five (5) subjects will consume the ACC after having a meal. The safety and the efficacy of the treatment will be closely monitored throughout this phase.

The absorption of ACC will be evaluated using weekly serum calcium corrected for albumin (CA) value tests. Excretion of calcium in urine will be tested at screening and at the end of phase I.

I-Day -21 (+/-17) Screening: Subjects with a diagnosed primary hypoparathyroidism (see section 4.1 for definitions), and who are treated with calcium and vitamin D supplementation at least 1 year prior to the beginning of the study and are without major renal or hepatic disease, will be invited to the Clinical Research Center. At the clinic, subjects will be interviewed, their medical history and their current medication will be documented and they will sign an informed consent form (ICF). Subjects will be referred to perform blood tests for serum calcium, P, creatinine and albumin levels. Calculation of albumin corrected calcium (CA) will be performed. Subjects will be instructed to perform 24 hour urine collection for Ca, P and creatinine. Subjects will be asked to fill out a food and medication diary for 3 consecutive days to evaluate their daily dietary calcium intake. Women of childbearing age will undergo a urine pregnancy test. Eligible subjects, complying with all inclusion criteria and having none of the exclusion criteria will be enrolled to the study.

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}



Original Primary Outcome: Calcium (albumin-corrected) serum level - composite value based on multiple measurments [ 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}



Current Secondary Outcome:

  • 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.

  • 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
  • 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.

  • 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.

  • 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).
  • 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

  • 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

  • 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

  • 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.

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

    The phosphate urine test measures the amount of phosphate in a samp

    Original Secondary Outcome:

    • 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.

    • Phosphorous serum level - composite value based on multiple measurments [ 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
    • 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.

    • 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.

    • Assessment of symptoms and signs related with hypocalcemia - composite value based on multiple measurments [ 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).
    • 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

    • 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

    • 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

    • 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.

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

      The phosphate urine test measures the amount of phosphate in a sample

      Information By: Amorphical Ltd.

      Dates:
      Date Received: March 7, 2013
      Date Started: April 2013
      Date Completion:
      Last Updated: March 30, 2015
      Last Verified: March 2015