Trial Outcomes & Findings for Ferric Citrate in Managing Serum Phosphorus and Iron Deficiency in Anemic Chronic Kidney Disease (CKD) Subjects Not on Dialysis (NCT NCT01736397)

NCT ID: NCT01736397

Last Updated: 2017-10-20

Results Overview

The difference in TSAT between the value at the end of treatment (week 12) minus the baseline measurement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

149 participants

Primary outcome timeframe

12 Weeks

Results posted on

2017-10-20

Participant Flow

Participant milestones

Participant milestones
Measure	Ferric Citrate Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit. Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit.	Placebo Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit. Placebo
Overall Study STARTED	75	74
Overall Study COMPLETED	61	50
Overall Study NOT COMPLETED	14	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Ferric Citrate Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit. Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit.	Placebo Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit. Placebo
Overall Study Lack of Efficacy	1	11
Overall Study Withdrawal by Subject	6	5
Overall Study Lost to Follow-up	0	1
Overall Study Adverse Event	6	3
Overall Study Not stated	1	4

Baseline Characteristics

Ferric Citrate in Managing Serum Phosphorus and Iron Deficiency in Anemic Chronic Kidney Disease (CKD) Subjects Not on Dialysis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ferric Citrate n=75 Participants Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit. Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit.	Placebo n=73 Participants Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit. Placebo	Total n=148 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=5 Participants	34 Participants n=7 Participants	65 Participants n=5 Participants
Age, Categorical >=65 years	44 Participants n=5 Participants	39 Participants n=7 Participants	83 Participants n=5 Participants
Age, Continuous	65.8 years STANDARD_DEVIATION 12.15 • n=5 Participants	64.5 years STANDARD_DEVIATION 13.55 • n=7 Participants	65.1 years STANDARD_DEVIATION 12.83 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	45 Participants n=7 Participants	96 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	28 Participants n=7 Participants	52 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	21 Participants n=7 Participants	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	60 Participants n=5 Participants	52 Participants n=7 Participants	112 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) White	59 Participants n=5 Participants	56 Participants n=7 Participants	115 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	75 Participants n=5 Participants	73 Participants n=7 Participants	148 Participants n=5 Participants
Chronic kidney disease (CKD), stage at baseline Stage III	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Chronic kidney disease (CKD), stage at baseline Stage IV	39 Participants n=5 Participants	39 Participants n=7 Participants	78 Participants n=5 Participants
Chronic kidney disease (CKD), stage at baseline Stage V	21 Participants n=5 Participants	17 Participants n=7 Participants	38 Participants n=5 Participants
Chronic kidney disease (CKD), stage at baseline Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 Weeks

Population: Efficacy analyses were based on Intent-to-Treat (ITT) population, which consisted of all randomized subjects who had a baseline laboratory value, had taken at least 1 dose of study drug, \& had at least 1 post-baseline laboratory value. ANCOVA with Last observation carried forward (LOCF) methodology was used.

The difference in TSAT between the value at the end of treatment (week 12) minus the baseline measurement.

Outcome measures

Outcome measures
Measure	Ferric Citrate n=72 Participants Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit. Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit.	Placebo n=69 Participants Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit. Placebo
Change in Transferrin Saturation (TSAT) From Baseline to End of Treatment Baseline	21.6 % saturation Standard Deviation 7.44	21.0 % saturation Standard Deviation 8.26
Change in Transferrin Saturation (TSAT) From Baseline to End of Treatment Week 12	31.7 % saturation Standard Deviation 14.19	20.0 % saturation Standard Deviation 7.55

PRIMARY outcome

Timeframe: 12 Weeks

Population: The efficacy analyses were based on the ITT population. The Intent-to-Treat (ITT) population consisted of all subjects who were randomized into the study, had a baseline laboratory value, had taken at least 1 dose of study drug, and had at least 1 post-baseline laboratory value. ANCOVA with LOCF methodology was used.

The difference in serum phosphorus between the value at the end of treatment (week 12) minus the baseline measurement.

Outcome measures

Outcome measures
Measure	Ferric Citrate n=72 Participants Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit. Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit.	Placebo n=69 Participants Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit. Placebo
Change in Serum Phosphorus Levels From Baseline to End of Treatment Baseline	4.5 mg/dL Standard Deviation 0.61	4.7 mg/dL Standard Deviation 0.60
Change in Serum Phosphorus Levels From Baseline to End of Treatment 12 weeks	3.9 mg/dL Standard Deviation 0.58	4.4 mg/dL Standard Deviation 0.75

SECONDARY outcome

Timeframe: 12 Weeks

The difference in ferritin levels between the value at the end of treatment (week 12) minus the baseline measurement.

Outcome measures

Outcome measures
Measure	Ferric Citrate n=72 Participants Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit. Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit.	Placebo n=69 Participants Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit. Placebo
Change in Ferritin Levels From Baseline to End of Treatment Baseline	115.8 ng/mL Standard Deviation 83.11	110.0 ng/mL Standard Deviation 80.88
Change in Ferritin Levels From Baseline to End of Treatment Week 12	189.4 ng/mL Standard Deviation 122.16	105.6 ng/mL Standard Deviation 93.87

SECONDARY outcome

Timeframe: 12 Weeks

The difference in hemoglobin levels between the value at the end of treatment (week 12) minus the baseline measurement.

Outcome measures

Outcome measures
Measure	Ferric Citrate n=72 Participants Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit. Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit.	Placebo n=69 Participants Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit. Placebo
Change in Hemoglobin Levels From Baseline to End of Treatment Baseline	10.5 g/dL Standard Deviation 0.81	10.6 g/dL Standard Deviation 1.07
Change in Hemoglobin Levels From Baseline to End of Treatment Week 12	11.0 g/dL Standard Deviation 1.03	10.4 g/dL Standard Deviation 1.14

Adverse Events

Ferric Citrate

Serious events: 6 serious events

Other events: 52 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 43 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Keryx Medical Information

Keryx Biopharmaceuticals

Phone: 1-844-44-KERYX (844-445-3799)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Ferric Citrate n=75 participants at risk Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit. Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit.	Placebo n=73 participants at risk Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit. Placebo
Cardiac disorders Atrial Fibrillation	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	0.00% 0/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Cardiac disorders Acute Coronary Syndrome	1.3% 1/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	0.00% 0/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Cardiac disorders Congestive Cardiac Failure	1.3% 1/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Cardiac disorders Cardiac Arrest	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
General disorders Chest Pain	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	2.7% 2/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Infections and infestations Pneumonia	1.3% 1/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	0.00% 0/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Infections and infestations Pyelonephritis	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Injury, poisoning and procedural complications Femoral Neck Fracture	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Investigations Haemoglobin decreased	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Renal and urinary disorders Renal Failure Acute	1.3% 1/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Renal and urinary disorders Renal Failure Chronic	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Respiratory, thoracic and mediastinal disorders COPD	1.3% 1/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Vascular disorders Accelerated Hypertension	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population

Measure	Ferric Citrate n=75 participants at risk Ferric citrate will be taken with or within one hour of meals or snacks. The dose of ferric citrate will depend on the patient's serum phosphorus results at each treatment visit. Ferric Citrate: Dose depends on serum phosphorus levels collected at each study visit.	Placebo n=73 participants at risk Placebo will be taken with or within one hour of meals or snacks. The number of placebo pills will depend on the patient's serum phosphorus results at each treatment visit. Placebo
Gastrointestinal disorders Faeces Discolored	32.0% 24/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	0.00% 0/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Gastrointestinal disorders Diarrhoea	20.0% 15/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	5.5% 4/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Gastrointestinal disorders Constipation	18.7% 14/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	5.5% 4/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Gastrointestinal disorders Nausea	6.7% 5/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	6.8% 5/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Gastrointestinal disorders Vomiting	5.3% 4/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	5.5% 4/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Infections and infestations Upper Respiratory Tract Infection	5.3% 4/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	0.00% 0/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Infections and infestations Urinary Tract Infection	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	5.5% 4/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Blood and lymphatic system disorders Anaemia	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Cardiac disorders Atrial Fibrillation	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	0.00% 0/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Gastrointestinal disorders Abdominal Discomfort	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Gastrointestinal disorders Abdominal Pain	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Gastrointestinal disorders Abdominal Pain Upper	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	2.7% 2/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Gastrointestinal disorders Dyspepsia	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	0.00% 0/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Gastrointestinal disorders Haemorrhoids	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	0.00% 0/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
General disorders Fatigue	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
General disorders Oedema	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
General disorders Oedema Peripheral	4.0% 3/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Injury, poisoning and procedural complications Foot Fracture	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Metabolism and nutrition disorders Gout	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	0.00% 0/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Metabolism and nutrition disorders Hyperglycaemia	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Metabolism and nutrition disorders Hyperkalaemia	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Metabolism and nutrition disorders Hypoglycaemia	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Nervous system disorders Dizziness	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	4.1% 3/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Nervous system disorders Dysgeusia	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	2.7% 2/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 1/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	4.1% 3/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Skin and subcutaneous tissue disorders Pruritis	1.3% 1/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	4.1% 3/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Skin and subcutaneous tissue disorders Rash	0.00% 0/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	2.7% 2/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population
Vascular disorders Hypertension	2.7% 2/75 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population	1.4% 1/73 • 12 weeks One subject on placebo was randomized but never received drug and so was excluded from the safety population