A Single Ascending Dose Study of Soluble Ferric Pyrophosphate Administered Intravenously in Healthy Volunteers.

NCT01920854 | Completed Phase 1 Results

• 1 other identifier: RMTI-SFP-9
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the pharmacokinetics of fixed ascending doses of intravenously administered Soluble Ferric Pyrophosphate

Conditions

Kidney Failure, Chronic Therapy; Hemodialysis

Keywords

Soluble Ferric Pyrophosphate, Pharmacokinetics, Iron, Hemodialysis

Outcome Measures

Primary Outcomes (11)

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 6 (Mean Total Serum Iron, Baseline Corrected)

  Serum iron for Cohorts 1-3, 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Serum iron for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 4, 5 (Mean Total Serum Iron, Baseline Corrected)

  Serum iron for Cohorts 1-3 and 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Serum iron for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 6 (Mean Transferrin-bound Iron, Baseline Corrected)

  Samples for transferrin-bound iron for Cohorts 1-3, 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Samples for transferrin-bound iron for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 4, 5 (Mean Transferrin-bound Iron, Baseline Corrected)

  Samples for transferrin-bound iron for Cohorts 1-3 and 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Samples for transferrin-bound iron for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 6 (Mean Total Iron Binding Capacity, Absolute)

  Samples for total iron binding capacity for Cohorts 1-3, 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Samples for total iron binding capacity for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 4, 5 (Mean Total Iron Binding Capacity, Absolute)

  Samples for total iron binding capacity for Cohorts 1-3 and 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Samples for total iron binding capacity for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 6 (Mean Non-transferrin Bound Iron, Baseline Corrected)

  Samples for non-transferrin bound iron for Cohorts 1-3, 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Samples for non-transferrin bound iron for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 4, 5 (Mean Non-transferrin Bound Iron, Baseline Corrected)

  Samples for non-transferrin bound iron for Cohorts 1-3 and 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Samples for non-transferrin bound iron for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 6 (Mean Unbound Iron Binding Capacity, Baseline Corrected)

  Samples for unbound iron binding capacity for Cohorts 1-3, 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Samples for unbound iron binding capacity for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Pharmacokinetics of Iron From Soluble Ferric Pyrophosphate: Cohorts 4, 5 (Mean Unbound Iron Binding Capacity, Baseline Corrected)

  Samples for unbound iron binding capacity for Cohorts 1-3 and 6 will be collected at 0, 0.5,1, 2, 3, 4, 4.5, 5, 6, 7, 7.5, 8, 9,10, 12,12.5 14, 16, 20, 24,36, and 48 hours. Samples for unbound iron binding capacity for Cohorts 4 and 5 will be collected at 0, 0.5,1, 2, 4, 6, 9, 12,12.5, 14,16,18,20, 24, 30, 36, and 48 hours. There was no formal sample size calculation for this study; 48 subjects were enrolled and 48 subjects were analyzed to establish the PK profile of the serum iron from SFP. Study results were summarized by dose group, with descriptive statistics. No additional statistical testing was performed. No imputation of missing data was performed. No windowing of visits was performed.

  48 hours

• Baseline Transferrin Profile: Cohorts 1, 2, 3, 4, 5, 6

  The mean baseline transferrin will be calculated based on samples drawn just prior to infusion for all Cohorts (both SFP and placebo)

  Baseline (1 day)

Secondary Outcomes (11)

• Serum Iron Profile From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 6 (Mean Absolute Transferrin Saturation, Calculated)

  48 hours

• Serum Iron Profile From Soluble Ferric Pyrophosphate: Cohorts 4, 5 (Mean Absolute Transferrin Saturation, Calculated)

  48 hours

• Serum Iron Profile From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 4, 5, 6 (Mean AUC [Area Under the Curve] 0 - 12, Mean AUC 0 - 4, Mean AUC Last)

  48 hours

• Serum Iron Profile From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 4, 5, 6 (Mean AUC [Area Under the Curve] Inf)

  48 hours

• Serum Iron Profile From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 4, 5, 6 (Mean CL [Clearance])

  48 hours

Study Arms (2)

Soluble Ferric Pyrophosphate

EXPERIMENTAL

Group/Cohort Designation: Ascending doses of SFP. Each subject will receive a defined dose of SFP IV administered under double-blind conditions. Pharmacokinetics of iron will be measured using a validated assay for iron and transferrin bound iron.

Drug: soluble ferric pyrophosphate

Control

PLACEBO COMPARATOR

Group/Cohort Designation: Each subject will receive placebo IV administered under double-blind conditions.

Drug: Placebo

Interventions

soluble ferric pyrophosphate DRUG

Also known as: SFP

Soluble Ferric Pyrophosphate

Placebo DRUG

Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or non-pregnant, non-lactating female who is at least 90 days post-partum.
• Subject is willing to comply with any applicable contraceptive requirements of the protocol.
• Satisfactory medical assessment with no clinically significant or relevant abnormalities in medical history, physical examination (PE), vital signs, electrocardiogram (ECG) and laboratory evaluation (hematology, biochemistry, urinalysis) as assessed by the Investigator.
• An understanding, ability and willingness to fully comply with study procedures and restrictions.
• Ability to provide written, personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations, before completing any study-related procedures.
• Subjects must agree to discontinue all iron preparations for 14 days prior to study drug administration.

You may not qualify if:

• Current or recurrent disease (e.g. cardiovascular, renal, liver, gastro-intestinal, malignancy or other conditions) that could affect the action, absorption or disposition of the investigational product utilized in this study, or could affect clinical or laboratory assessments.
• Hemoglobin \< 11 g/dL or Hematocrit \< 30%.
• Serum iron concentration ≤ 70 µg/dL (male or female).
• Current or relevant previous history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or study procedures.
• Significant illness, as judged by the investigator, within 2 weeks of the first dose of investigational product.
• Current use of any medication (including prescription, over the counter \[OTC\], herbal or homeopathic preparations) within 14 days of first dose of investigational product. Exceptions are hormonal replacement therapy, hormonal contraceptives, acetaminophen and non-steroidal anti-inflammatory drugs.
• Known or suspected intolerance or hypersensitivity to iron containing product(s).
• History of alcohol or other substance abuse within the last year.
• A positive screen for cotinine, alcohol or drugs of abuse.
• Male subjects who consume more than 21 units of alcohol per week or three units per day. Female subjects who consume more than 14 units of alcohol per week or two units per day. 1 alcohol unit =1 beer = 1 wine (5oz) = 1 liquor (1.5 oz.).
• A history of a positive human immunodeficiency virus (HIV) antibody screen, Hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) antibody screen.
• Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g. gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.
• Routine consumption of more than five units of caffeine per day or subjects who experience caffeine withdrawal headaches. One caffeine unit is contained in the following items: one 6-oz. cup of coffee, two 12-oz. cans of cola, one 12-oz. cup of tea, three 1-oz. chocolate bars.
• Donation of blood or blood products (e.g., plasma or platelets) within 60 days prior to receiving the first dose of investigational product.
• Use of another investigational product within 30 days prior to receiving the first dose of investigational product or active enrolment in another drug or vaccine clinical study.

Sponsors & Collaborators

• Rockwell Medical Technologies, Inc.: lead

Study Sites (1)

Unknown Facility

Kalamazoo, Michigan, 49007, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

spleen fibrinolytic proteinase (human)

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Senior Director, Clinical Research & Operations
• Organization: Rockwell Medical

rd@rockwellmed.com

248-960-9009

Study Officials

• Raymond D Pratt, MD FACP

  Rockwell Medical Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2013
• First Posted: August 12, 2013
• Study Start: June 1, 2013
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: January 26, 2015
• Results First Posted: December 19, 2014

Record last verified: 2015-01

Locations

US (1)