A Blinded, Placebo-Controlled Study of the Safety and Pharmacokinetics of Single Doses of Intravenous Deferiprone in Healthy Volunteers

• Sponsor: ApoPharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01989455
• Collaborator: (none)
• Enrollment: 64
• Location: 1
• Arms: 4
• Duration (Months): 3.9
• Patients Per Site Per Month: 16.2

Study Details

Study Description

Brief Summary

Single center, randomized, double-blind, placebo-controlled, adaptive sequential ascending-dose study for the evaluation of the safety, tolerability, and pharmacokinetics of single doses of deferiprone administered by intravenous infusion to healthy males and females. A bioavailability comparison will be included.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Deferiprone; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Official Title: A Single Center, Phase I, Double-blind, Placebo-controlled Evaluation of the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of Deferiprone Administered by Intravenous Infusion to Healthy Male and Female Volunteers
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Single dose of 500mg deferiprone or placebo administered via intravenous infusion. First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo. Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo.	Drug: Deferiprone; Deferiprone for infusion, 10mg/mL for intravenous infusion. Oral dose of deferiprone: 80mg/mL oral solution. (Cohort 2); Other Names: Ferriprox DFP L1 ; Drug: Placebo; Placebo: normal saline solution.; Other Names: Saline solution.
Experimental: Cohort 2 Single dose of 1000mg deferiprone or placebo administered via intravenous infusion and oral solution. Randomization will be done for all 16 subjects at the same time: 14 will be randomized to receive deferiprone and 2 to receive placebo. Subjects enrolled to cohort 2 will receive an oral dose of deferiprone.	Drug: Deferiprone; Deferiprone for infusion, 10mg/mL for intravenous infusion. Oral dose of deferiprone: 80mg/mL oral solution. (Cohort 2); Other Names: Ferriprox DFP L1 ; Drug: Placebo; Placebo: normal saline solution.; Other Names: Saline solution.
Experimental: Cohort 3 Single dose of 1500mg deferiprone or placebo administered via intravenous infusion. Randomization will be done for all 16 subjects at the same time, 14 will be randomized to receive deferiprone and 2 to receive placebo.	Drug: Deferiprone; Deferiprone for infusion, 10mg/mL for intravenous infusion. Oral dose of deferiprone: 80mg/mL oral solution. (Cohort 2); Other Names: Ferriprox DFP L1 ; Drug: Placebo; Placebo: normal saline solution.; Other Names: Saline solution.
Experimental: Cohort 4 Single dose of 2000mg deferiprone or placebo administered via intravenous infusion. First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo. Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo.	Drug: Deferiprone; Deferiprone for infusion, 10mg/mL for intravenous infusion. Oral dose of deferiprone: 80mg/mL oral solution. (Cohort 2); Other Names: Ferriprox DFP L1 ; Drug: Placebo; Placebo: normal saline solution.; Other Names: Saline solution.

Outcome Measures

Primary Outcome Measures

1. Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide [14-hour interval]

   Cmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

2. Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide [14-hour interval]

   Tmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose. The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation).

3. Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide [14-hour interval]

   AUC0-∞ was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

4. The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide [14-hour interval]

   T1/2el was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

5. Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers. [From start of intravenous dosing until Day 5 post-dose for all subjects; and from time of oral dose until 24 hours post-dose for subjects who additionally received oral deferiprone]

   The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of intravenous deferiprone.

Secondary Outcome Measures

1. Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone [14-hour interval]

   Cmax was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

2. Absolute Bioavailability of Deferiprone [14-hour interval]

   The pharmacokinetic profile was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

3. Safety and Tolerability of a Single 1000 mg Oral Dose of Deferiprone [From dosing until 24 hours post-dose]

   The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of oral deferiprone. Note: All subjects in the 1000 mg cohort received active product, including the 2 who had received placebo for the intravenous infusion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Main Inclusion Criteria:

1. Healthy adult males or females, at least 18 years old but not older than 50 years.

2. Body weight at least 60kg.

3. Body Mass Index (BMI) ≥ 18.50 and ≤ 30.00 kg/m2

4. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, ECG, vital signs, physical examination.

5. Non or ex-smoker (someone who has completely stopped smoking 6 months before study start)

6. For females, negative result on a serum pregnancy test.

Main Exclusion Criteria:

1. Absolute neutrophil count (ANC) <1.5x10^9/L.

2. History or presence of hypersensitivity to deferiprone or any related products.

3. History or presence of gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs.

4. Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease.

5. Any history of tuberculosis (TB) or prophylaxis for TB.

6. Suicidal tendency, history of seizures, head trauma with coma or craniotomy/trepanation, state of confusion or relevant psychiatric disease.

7. Inadequate venous access in either arm.

8. Presence of out-of-range cardiac interval or clinically significant ECG abnormalities (PR <110 msec or > 220 msec, QRS <60 msec or >119 msec, QTcB > 450 msec for males and

460 msec for females).

1. Use of acetaminophen, acetylsalicylic acid (ASA), or non-steroidal anti-inflammatory drugs (NSAIDs) in the previous 7 days before study start.

2. Use of any enzyme-modifying drugs, including strong inhibitors of P450 (CYP) enzymes such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals OR strong inducers of CYP enzymes such as: barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, and St. John's wart within 28 days prior to study start.

3. Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse.

4. Had a clinically significant illness during the 28 days prior to study start.

5. Receipt of an investigational product in another clinical trial within 28 days prior prior to study start.

6. Enrolment in a previous cohort of this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Algorithme Pharma Inc.	Mont-Royal	Quebec	Canada	H3P3P1

Sponsors and Collaborators

• ApoPharma

Investigators

• Study Chair: Fernando Tricta, MD, ApoPharma Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ApoPharma
• ClinicalTrials.gov Identifier: NCT01989455
• Other Study ID Numbers: LA42-0113
• First Posted: Nov 21, 2013
• Last Update Posted: Dec 23, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by ApoPharma: Healthy; Deferiprone; DFP; L1
• Additional relevant MeSH terms: Deferiprone

Study Results

Participant Flow

Arm/Group Title	500 mg Deferiprone	1000 mg Deferiprone	1500 mg Deferiprone	2000 mg Deferiprone	Placebo
Arm/Group Description	Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL), followed one week later by a single oral dose of 1000 mg deferiprone oral solution, 80 mg/mL	Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of placebo (normal saline solution).
Period Title: Overall Study
STARTED	14	14	14	14	8
COMPLETED	14	12	13	14	7
NOT COMPLETED	0	2	1	0	1

Baseline Characteristics

Arm/Group Title	500 mg Deferiprone for Infusion	1000 mg Deferiprone for Infusion	1500 mg Deferiprone for Infusion	2000 mg Deferiprone for Infusion	Placebo	Total
Arm/Group Description	Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of placebo (normal saline solution).	Total of all reporting groups
Overall Participants	14	14	14	14	8	64
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	14 100%	14 100%	14 100%	14 100%	8 100%	64 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 7.1%	4 28.6%	6 42.9%	6 42.9%	4 50%	21 32.8%
Male	13 92.9%	10 71.4%	8 57.1%	8 57.1%	4 50%	43 67.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 7.1%	1 7.1%	0 0%	0 0%	0 0%	2 3.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 7.1%	2 14.3%	1 7.1%	3 21.4%	1 12.5%	8 12.5%
White	12 85.7%	11 78.6%	13 92.9%	11 78.6%	7 87.5%	54 84.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Canada	14 100%	14 100%	14 100%	14 100%	8 100%	64 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide
Description	Cmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time Frame	14-hour interval

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	500 mg Deferiprone for Infusion	1000 mg Deferiprone for Infusion	1500 mg Deferiprone for Infusion	2000 mg Deferiprone for Infusion
Arm/Group Description	Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL)
Measure Participants	14	13	13	14
Cmax for serum deferiprone	7.406 (1.889)	17.835 (2.162)	27.749 (2.768)	36.644 (6.643)
Cmax for serum deferiprone-3-O-glucuronide	8.037 (1.374)	16.490 (4.348)	20.032 (3.757)	30.517 (3.947)

2. Primary Outcome

Title	Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide
Description	Tmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose. The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation).
Time Frame	14-hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	500 mg Deferiprone for Infusion	1000 mg Deferiprone for Infusion	1500 mg Deferiprone for Infusion	2000 mg Deferiprone for Infusion
Arm/Group Description	Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL)
Measure Participants	14	13	13	14
Tmax for Serum Deferiprone	1.00	1.00	1.00	1.00
Tmax for Serum Deferiprone 3-O-glucuronide	2.50	2.50	2.50	2.50

3. Primary Outcome

Title	Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide
Description	AUC0-∞ was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time Frame	14-hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	500 mg Deferiprone for Infusion	1000 mg Deferiprone for Infusion	1500 mg Deferiprone for Infusion	2000 mg Deferiprone for Infusion
Arm/Group Description	Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL)
Measure Participants	14	13	14	14
AUC0-∞ for serum deferiprone	18.326 (4.115)	41.805 (6.797)	69.390 (8.937)	89.250 (17.223)
AUC0-∞ for serum deferiprone 3-O-glucuronide	38.504 (8.011)	79.210 (15.686)	105.829 (13.052)	161.507 (16.876)

4. Primary Outcome

Title	The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide
Description	T1/2el was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time Frame	14-hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	500 mg Deferiprone for Infusion	1000 mg Deferiprone for Infusion	1500 mg Deferiprone for Infusion	2000 mg Deferiprone for Infusion
Arm/Group Description	Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL)
Measure Participants	14	13	13	14
T1/2el for serum deferiprone	1.68 (0.22)	1.77 (0.32)	1.83 (0.22)	1.85 (0.17)
T1/2el for serum deferiprone 3-O-glucuronide	2.00 (0.25)	1.94 (0.25)	2.01 (0.18)	1.94 (0.26)

5. Primary Outcome

Title	Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers.
Description	The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of intravenous deferiprone.
Time Frame	From start of intravenous dosing until Day 5 post-dose for all subjects; and from time of oral dose until 24 hours post-dose for subjects who additionally received oral deferiprone

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received study product.

Arm/Group Title	500 mg Deferiprone for Infusion	1000 mg Deferiprone for Infusion	1500 mg Deferiprone for Infusion	2000 mg Deferiprone for Infusion	Placebo
Arm/Group Description	Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single intravenous dose of placebo (normal saline solution).
Measure Participants	14	14	14	14	8
Number [participants]	10 71.4%	7 50%	8 57.1%	10 71.4%	3 37.5%

6. Secondary Outcome

Title	Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone
Description	Cmax was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time Frame	14-hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	1000 mg Deferiprone for Infusion	1000 mg Oral Deferiprone
Arm/Group Description	Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single oral dose of 1000 mg deferiprone (deferiprone oral solution, 80 mg/mL)
Measure Participants	14	12
Cmax for serum deferiprone	17.835 (2.162)	11.692 (3.436)
Cmax for serum deferiprone-3-O-glucuronide	16.490 (4.348)	18.806 (5.659)

7. Secondary Outcome

Title	Absolute Bioavailability of Deferiprone
Description	The pharmacokinetic profile was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.
Time Frame	14-hour interval

Outcome Measure Data

Analysis Population Description

The pharmacokinetic population included all subjects who had sufficient data to derive the value of at least one pharmacokinetic parameter.

Arm/Group Title	1000 mg Deferiprone for Infusion	1000 mg Oral Deferiprone
Arm/Group Description	Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)	Single oral dose of 1000 mg deferiprone (deferiprone oral solution, 80 mg/mL)
Measure Participants	13	12
Mean (Standard Deviation) [μg*h/mL]	41.805 (6.797)	30.796 (7.182)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	500 mg Deferiprone for Infusion, 1000 mg Deferiprone for Infusion
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percent ratio
	Estimated Value	73.19
	Confidence Interval	(2-Sided) 90%; 68.83 to 77.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Safety and Tolerability of a Single 1000 mg Oral Dose of Deferiprone
Description	The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of oral deferiprone. Note: All subjects in the 1000 mg cohort received active product, including the 2 who had received placebo for the intravenous infusion.
Time Frame	From dosing until 24 hours post-dose

Outcome Measure Data

Analysis Population Description

The safety population included all subjects who received study product.

Arm/Group Title	1000 mg Oral Deferiprone
Arm/Group Description	Single oral dose of 1000 mg deferiprone (deferiprone oral solution, 80 mg/mL)
Measure Participants	14
Number [participants]	2 14.3%

Adverse Events

Arm/Group Title	500 mg Deferiprone for Infusion		1000 mg Deferiprone for Infusion		1500 mg Deferiprone for Infusion		2000 mg Deferiprone for Infusion		Placebo		1000 mg Oral Deferiprone
Arm/Group Description	Single intravenous dose of 500 mg deferiprone (deferiprone for infusion, 10 mg/mL)		Single intravenous dose of 1000 mg deferiprone (deferiprone for infusion, 10 mg/mL)		Single intravenous dose of 1500 mg deferiprone (deferiprone for infusion, 10 mg/mL)		Single intravenous dose of 2000 mg deferiprone (deferiprone for infusion, 10 mg/mL)		Single intravenous dose of placebo (normal saline solution).		Single oral dose of 1000 mg deferiprone (deferiprone oral solution, 80 mg/mL)
All Cause Mortality
	500 mg Deferiprone for Infusion		1000 mg Deferiprone for Infusion		1500 mg Deferiprone for Infusion		2000 mg Deferiprone for Infusion		Placebo		1000 mg Oral Deferiprone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	500 mg Deferiprone for Infusion		1000 mg Deferiprone for Infusion		1500 mg Deferiprone for Infusion		2000 mg Deferiprone for Infusion		Placebo		1000 mg Oral Deferiprone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)		0/14 (0%)		0/14 (0%)		0/8 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	500 mg Deferiprone for Infusion		1000 mg Deferiprone for Infusion		1500 mg Deferiprone for Infusion		2000 mg Deferiprone for Infusion		Placebo		1000 mg Oral Deferiprone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/14 (71.4%)		7/14 (50%)		8/14 (57.1%)		10/14 (71.4%)		3/8 (37.5%)		2/14 (14.3%)
Gastrointestinal disorders
Nausea	1/14 (7.1%)	1	1/14 (7.1%)	1	1/14 (7.1%)	1	2/14 (14.3%)	2	0/8 (0%)	0	1/14 (7.1%)	1
Vomiting	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0	1/8 (12.5%)	1	0/14 (0%)	0
Diarrhoea	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/8 (12.5%)	1	0/14 (0%)	0
General disorders
Fatigue	2/14 (14.3%)	2	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0
Feeling hot	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0
Feeling of body temperature change	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/8 (0%)	0	0/14 (0%)	0
Injury, poisoning and procedural complications
Catheter site swelling	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0
Procedural complication	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/8 (0%)	0	0/14 (0%)	0
Procedural dizziness	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/8 (0%)	0	0/14 (0%)	0
Vessel puncture site pain	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0
Vessel puncture site reaction	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0
Catheter site pain	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/8 (12.5%)	1	0/14 (0%)	0
Investigations
C-reactive protein increased	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/8 (0%)	0	0/14 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/14 (14.3%)	2	1/14 (7.1%)	1	1/14 (7.1%)	1	1/14 (7.1%)	1	0/8 (0%)	0	0/14 (0%)	0
Nervous system disorders
Somnolence	8/14 (57.1%)	9	5/14 (35.7%)	5	4/14 (28.6%)	4	5/14 (35.7%)	5	0/8 (0%)	0	1/14 (7.1%)	1
Headache	4/14 (28.6%)	4	4/14 (28.6%)	4	3/14 (21.4%)	3	4/14 (28.6%)	5	0/8 (0%)	0	1/14 (7.1%)	1
Dizziness	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/8 (0%)	0	0/14 (0%)	0
Head discomfort	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/8 (0%)	0	0/14 (0%)	0
Hypoaesthesia	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0
Vertigo	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dysphonia	0/14 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/14 (7.1%)	1	0/8 (0%)	0	0/14 (0%)	0
Sneezing	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0
Skin and subcutaneous tissue disorders
Erythema	0/14 (0%)	0	0/14 (0%)	0	2/14 (14.3%)	2	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0
Generalized erythema	0/14 (0%)	0	1/14 (7.1%)	1	0/14 (0%)	0	0/14 (0%)	0	0/8 (0%)	0	0/14 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.