Study to Evaluate the Efficacy and Safety of PT20 in Subjects With Hyperphosphataemia and Dialysis Dependent Chronic Kidney Disease

Study Overview
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Brief Summary
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The main purpose of this study is to see whether PT20 can help people with a high level of phosphate in their blood (called Hyperphosphatemia) that are being treated with dialysis for kidney disease.

Detailed Description
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PT20 represents a mechanism to address many of the limitations associated with current phosphate binding agents. The available clinical and non clinical evidence suggests that PT20 binds phosphate and prevents its uptake more efficiently than other phosphate binding drugs and may therefore either reduce the pill burden associated with controlling phosphate levels, or result in lower phosphate levels with the same pill burden. The this study is the first to investigate the efficacy and safety of PT20 in subjects with dialysis-dependent chronic kidney disease (CKD).

Official Title
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Study to Evaluate the Efficacy and Safety of PT20 in Subjects With Hyperphosphataemia and Dialysis Dependent Chronic Kidney Disease

Conditions
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Hyperphosphataemia

Intervention / Treatment
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* Drug: PT20
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 18 90 years Subject must have a stable dialysis prescription for at least 28 days prior to start of Screening. Subject must have the most recent serum phosphate measurement, taken during the 28 days prior to the start of Screening, of ≥ 4.0 mg/dL and ≤ 8 mg/dL. Exclusion Criteria: Subject's most recent historical pre-dialysis serum bicarbonate value within 14 days prior to the start of Screening (Visit 1) is < 18 mg/dL. Subject has, in the opinion of the investigator, severe chronic lung disease and/or carbon dioxide retention.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - PT20 400 mg tid<br>PT20 400 mg tid (1.2 g/day) administered orally. Dosing was initiated with the subject's first meal/snack following receipt of study medication at Visit 7 (Day 1). There was to be no change in dose administration level with respect to each cohort in this study | Drug: PT20<br>* Modified ferric oxide adipate tablets<br>* Other names: M10L78;|
| Experimental: Group 2 - PT20 800 mg tid<br>PT20 800 mg tid (2.4 g/day) administered orally. Dosing was initiated with the subject's first meal/snack following receipt of study medication at Visit 7 (Day 1). There was to be no change in dose administration level with respect to each cohort in this study | Drug: PT20<br>* Modified ferric oxide adipate tablets<br>* Other names: M10L78;|
| Experimental: Group 3 - PT20 1600 mg tid<br>PT20 1600 mg tid (4.8 g/day) administered orally. Dosing was initiated with the subject's first meal/snack following receipt of study medication at Visit 7 (Day 1). There was to be no change in dose administration level with respect to each cohort in this study | Drug: PT20<br>* Modified ferric oxide adipate tablets<br>* Other names: M10L78;|
| Experimental: Group 4 - PT20 3200 mg tid<br>PT20 3200 mg tid (9.6 g/day) administered orally. Dosing was initiated with the subject's first meal/snack following receipt of study medication at Visit 7 (Day 1). There was to be no change in dose administration level with respect to each cohort in this study | Drug: PT20<br>* Modified ferric oxide adipate tablets<br>* Other names: M10L78;|
| Placebo Comparator: Group 5 - Placebo tid<br>Matched Placebo (for PT20) tid administered orally. Dosing was initiated with the subject's first meal/snack following receipt of study medication at Visit 7 (Day 1). There was to be no change in dose administration level with respect to each cohort in this study | Drug: Placebo<br>* Placebo tablets matched to each PT20 dose arm<br>* Other names: Matched Placebo for PT20;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Phosphate Concentration From Baseline (Visit 7, Day 1) to Visit 11 (Day 29) | The primary efficacy endpoint was the change in serum phosphate concentration from Baseline (Visit 7, Day 1) to Visit 11 (Day 29). All study specific blood samples were collected, processed and analysed using a central laboratory. | Day 1 to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Haemoglobin Concentration From Baseline (Visit 7, Day 1) to Visit 11 (Day 29) | Descriptive statistics were to be used to summarise values and change from Baseline (Visit 7, Day 1) to Day 29 (Visit 11) in haemoglobin concentration. An analysis of covariance (ANCOVA) was to be used to analyse the changes from Baseline (Visit 7, Day 1) to Visit 11 (Day 29), which were to include the fixed, categorical effects of treatment as well as the continuous, fixed covariates of Baseline concentrations for haemoglobin. Only those subjects with available concentrations for both Baseline (Visit 7, Day 1) and Visit 11 (Day 29) were to be included in this analysis. | Day 1 to Day 29 | 
| Change in Serum Ferritin Concentration From Baseline (Visit 7, Day 1) to Visit 11 (Day 29) | Descriptive statistics were to be used to summarise values and change from Baseline (Visit 7, Day 1) to Day 29 (Visit 11) in serum ferritin concentration. An analysis of covariance (ANCOVA) was to be used to analyse the changes from Baseline (Visit 7, Day 1) to Visit 11 (Day 29), which were to include the fixed, categorical effects of treatment and week (Visit), as well as the continuous, fixed covariates of Baseline concentrations for serum ferritin. Only those subjects with available concentrations for both Baseline (Visit 7, Day 1) and Visit 11 (Day 29) were to be included in this analysis. | Day 1 to Day 29 | 
| Change in Transferrin Saturation From Baseline (Visit 7, Day 1) to Visit 11 (Day 29) | Descriptive statistics were to be used to summarise values and change from Baseline (Visit 7, Day 1) to Day 29 (Visit 11) in transferrin saturation. An analysis of covariance (ANCOVA) was to be used to analyse the changes from Baseline (Visit 7, Day 1) to Day 29 (Visit 11), which were to include the fixed, categorical effects of treatment and week, as well as the continuous, fixed covariates of Baseline concentrations for transferrin saturation. Only those subjects with available concentrations for both Baseline (Visit 7, Day 1) and Visit 11 (Day 29) were to be included in this analysis. | Day 1 to Day 29 | 
| Change in Calcium x Phosphate Product From Baseline (Visit 7, Day 1) to Visit 11 (Day 29) | Descriptive statistics were to be used to summarise values and change from Baseline (Visit 7, Day 1) to Day 29 (Visit 11) in Calcium x Phosphate Product . An analysis of covariance (ANCOVA) was to be used to analyse the changes from Baseline (Visit 7, Day 1) to Day 29 (Visit 11), which were to include the fixed, categorical effects of treatment, as well as the continuous, fixed covariates of Baseline concentrations for Calcium x Phosphate Product. Only those subjects with available concentrations for both Baseline (Visit 7, Day 1) and Visit 11 (Day 29) were to be included in this analysis. In CKD subjects (Stages 3-5), the clinical recommendation (KDOQI) is that serum calcium x phosphate product should be maintained at < 55 mg^2/dL^2 (4.4 mmol^2 /L^2). | Day 1 to Day 29 | 
| Change in Gastrointestinal Symptom Rating System (GSRS) Overall Score From Baseline (Visit 7, Day 1) to Visit 11 (Day 29) | The GSRS assesses the impact of treatment-related GI complications. It includes 15 items divided into 5 subscales (diarrhoea, indigestion, abdominal pain, constipation, and reflux), and uses a seven-grade Likert scale to assess symptoms (1 = no discomfort at all, 7 = very severe discomfort). The total score was calculated as the average score of all 15 items. If data were missing from one or more subscales, the mean of the completed items within the subscale was to be used for the subscale score, provided that more than half of the subscale items were complete. If more than half of the items within a subscale were missing, the subscale score and overall score were also to be defined as missing. The change in overall GSRS score from Baseline (Visit 7, Day 1) to Visit 11 (Day 29) was summarised by treatment and a two-sample t-test was to be used to identify differences between the placebo and PT20 dose groups. The higher the score, the more severe the gastrointestinal symptoms. | Day 1 to Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dialysis Dependent Chronic Kidney Disease