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.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Calcium (albumin-corrected) serum level - composite value based on multiple measurements
研究概览
简要总结
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.
详细描述
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.
Subjects will be informed by phone or on site whether they are eligible to enter the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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:
- •Anticonvulsants
- •Carbonic anhydrase
- •Adrenocorticosteroids
- •Subjects who are non-cooperative or unwilling to sign consent form.
- •Pregnant or breast-feeding women.
结局指标
主要结局
Calcium (albumin-corrected) serum level - composite value based on multiple measurements
时间窗: 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}
次要结局
- Urine phosphorus level - 24h urine collection(Phase II: termination of study (Day 70))
- 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)
- Urine creatinine level - 24h urine collection(Phase II: termination of study (Day 70))
- 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)