A Single Ascending Dose Study of Soluble Ferric Pyrophosp... | NCT01920854

NCT01920854

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
soluble ferric pyrophosphate	Drug		Soluble Ferric Pyrophosphate	SFP
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.

Secondary Outcomes

Measure	Description	Time Frame
Serum Iron Profile From Soluble Ferric Pyrophosphate: Cohorts 1, 2, 3, 6 (Mean Absolute Transferrin Saturation, Calculated)	Samples for transferrin saturation 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 saturation 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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age 18-55 inclusive at the time of consent. This inclusion criterion will only be assessed at the first screening visit.
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.
Body Mass Index (BMI) between 20.0 and 32.0 kg/m² inclusive. This inclusion criterion will only be assessed at the first screening visit.
Subjects must agree to discontinue all iron preparations for 14 days prior to study drug administration.

Exclusion Criteria:

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.
Pregnancy or intention to become pregnant before completing all study drug treatment.
Current medical status that, in the investigators opinion, would preclude participation in the study.

Name	Affiliation	Role
Raymond D Pratt, MD FACP	Rockwell Medical Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Kalamazoo	Michigan	49007	United States

Arm/Group Information

ID	Title	Description
FG000	Cohorts 1 - 6 Placebo	A total of 48 subjects were studied in 6 sequential cohorts (8 subjects per group, randomized as 6 active and 2 placebo). Cohorts 1, 2, 3, and 6 received ascending doses of test article over 4-hour infusions. Cohorts 4 and 5 received ascending doses of test article over 12-hour infusions. Cohorts 1 - 6 Placebo received IV D5W infused over either 4 hours (Cohorts 1, 2, 3, 6) or 12 hours (Cohorts 4, 5).
FG001	Cohort 1 SFP	A total of 48 subjects were studied in 6 sequential cohorts (8 subjects per group, randomized as 6 active and 2 placebo). Cohorts 1, 2, 3, and 6 received ascending doses of test article over 4-hour infusions. Cohorts 4 and 5 received ascending doses of test article over 12-hour infusions. Cohort 1 SFP received 2.5 mg IV SFP infused over 4 hours.
FG002	Cohort 2 SFP	A total of 48 subjects were studied in 6 sequential cohorts (8 subjects per group, randomized as 6 active and 2 placebo). Cohorts 1, 2, 3, and 6 received ascending doses of test article over 4-hour infusions. Cohorts 4 and 5 received ascending doses of test article over 12-hour infusions. Cohort 2 SFP received 5.0 mg IV SFP infused over 4 hours.
FG003	Cohort 3 SFP	A total of 48 subjects were studied in 6 sequential cohorts (8 subjects per group, randomized as 6 active and 2 placebo). Cohorts 1, 2, 3, and 6 received ascending doses of test article over 4-hour infusions. Cohorts 4 and 5 received ascending doses of test article over 12-hour infusions. Cohort 3 SFP received 7.5 mg IV SFP infused over 4 hours.
FG004	Cohort 4 SFP	A total of 48 subjects were studied in 6 sequential cohorts (8 subjects per group, randomized as 6 active and 2 placebo). Cohorts 1, 2, 3, and 6 received ascending doses of test article over 4-hour infusions. Cohorts 4 and 5 received ascending doses of test article over 12-hour infusions. Cohort 4 SFP received 15 mg IV SFP infused over 12 hours.
FG005	Cohort 5 SFP	A total of 48 subjects were studied in 6 sequential cohorts (8 subjects per group, randomized as 6 active and 2 placebo). Cohorts 1, 2, 3, and 6 received ascending doses of test article over 4-hour infusions. Cohorts 4 and 5 received ascending doses of test article over 12-hour infusions. Cohort 5 SFP received 20 mg IV SFP infused over 12 hours.
FG006	Cohort 6 SFP	A total of 48 subjects were studied in 6 sequential cohorts (8 subjects per group, randomized as 6 active and 2 placebo). Cohorts 1, 2, 3, and 6 received ascending doses of test article over 4-hour infusions. Cohorts 4 and 5 received ascending doses of test article over 12-hour infusions. Cohort 6 SFP received 10 mg IV SFP infused over 4 hours.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Cohorts 1 - 6 Placebo	A total of 48 subjects were studied in 6 sequential cohorts (8 subjects per group, randomized as 6 active and 2 placebo). Cohorts 1, 2, 3, and 6 received ascending doses of test article over 4-hour infusions. Cohorts 4 and 5 received ascending doses of test article over 12-hour infusions. Cohorts 1 - 6 Placebo received IV D5W infused over either 4 hours (Cohorts 1, 2, 3, 6) or 12 hours (Cohorts 4, 5).

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

The PK Population was defined as all subjects receiving a dose of SFP or placebo who had sufficient post-dose blood samples taken to estimate PK parameters for serum iron endpoints. All 48 enrolled subjects were included in the PK Population.

Posted

Mean

Standard Deviation

micrograms/dL

48 hours

ID	Title	Description

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohorts 1 - 6 Placebo	A total of 48 subjects were studied in 6 sequential cohorts (8 subjects per group, randomized as 6 active and 2 placebo). Cohorts 1, 2, 3, and 6 received ascending doses of test article over 4-hour infusions. Cohorts 4 and 5 received ascending doses of test article over 12-hour infusions. Cohorts 1 - 6 Placebo received IV D5W infused over either 4 hours (Cohorts 1, 2, 3, 6) or 12 hours (Cohorts 4, 5).

ID	Term
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications