The Effect of Food on the Bioavailability of a Single Dose of SSP-004184SS in Healthy Adult Subjects

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01905553
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arms: 2
• Actual Duration (Days): 28
• Patients Per Site Per Month: 9.8

Study Details

Study Description

Brief Summary

To assess the effect of food on the pharmacokinetic profile of SSP-004184 compared to administration under fasted conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: SSP-004184SS	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-label, Randomized, 2-period, Crossover, Exploratory Study to Investigate the Effect of Food on the Bioavailability of a Single Dose of SSP-004184SS in Healthy Adult Subjects
• Actual Study Start Date: Aug 27, 2013
• Actual Primary Completion Date: Sep 24, 2013
• Actual Study Completion Date: Sep 24, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SSP-004184SS (fed) 21.8 mg/kg (oral capsule form) given once on Day 1 under fed conditions	Drug: SSP-004184SS; Disodium salt; Other Names: SPD602
Experimental: SSP-004184SS (fasted) 21.8 mg/kg (oral capsule form) given once on Day 1 under fasted conditions	Drug: SSP-004184SS; Disodium salt; Other Names: SPD602

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 Under Fasted and Fed Conditions [Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours.]

   AUCinf is the area under the plasma concentration versus time curve from time 0 to infinity. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

2. Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of SSP-004184 Under Fed and Fasted Conditions [Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours.]

   AUClast is the area under the curve from the time of dosing to the last measurable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

3. Maximum Plasma Concentration (Cmax) of SSP-004184 Under Fed and Fasted Conditions [Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours.]

   Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age 18-65 years inclusive at the time of consent. The date of signing informed consent is defined as the beginning of the Screening Period. This inclusion criterion will only be assessed at the Screening Visit.

• Subject is considered "healthy". Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis.

• Serum ferritin >20ng/mL, hemoglobin >125g/l, and erythrocyte indices within normal range of the clinical laboratory at the Screening Visit and on Day -1: packed cell volume, mean corpuscular volume, and mean corpuscular hemoglobin concentration, or deemed not clinically significant by the investigator.

• Subject is willing to comply with any applicable contraceptive requirements of the protocol and is:

• Male, or

• Female of non-childbearing potential (defined as a female who is post-menopausal [amenorrhea for at least 12 consecutive months] or surgically sterile [hysterectomy, bilateral tubal ligation, bilateral oophorectomy, or bilateral salpingectomy]) and at least 6 weeks post-sterilization

• Non-pregnant, non-lactating female

• At least 90 days post-partum or nulliparous (females only).

• 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 International Conference on Harmonisation Good Clinical Practice Guideline E6 (1996) and applicable regulations, before completing any study-related procedures.

• Body mass index between 18.5-30.0kg/m² inclusive. This inclusion criterion will be assessed only at the Screening Visit.

• Ability to swallow the investigational product (multiple capsules at 1 time or consecutively 1 capsule at a time).

Exclusion Criteria:

• A clinically significant history or disorder detected during the medical interview/physical examination such as any cardiovascular, bronchopulmonary, gastrointestinal (eg, inflammatory bowel disease, chronic diarrhea), hepatic, biliary (including gall bladder removal), renal, hematological, endocrine, autoimmune, neurological, or psychiatric disease (including depression) or any other medical condition that is capable of altering the absorption, metabolism, or elimination of drugs; or of constituting a risk factor when taking the investigational product in the judgment of the investigator.

• Confirmed systolic blood pressure >139mmHg or <89mmHg, and diastolic blood pressure

89mmHg or <49mmHg.

• Twelve-lead ECG demonstrating QTc >450msec at screening. If QTc exceeds 450msec, the ECG should be repeated 2 more times and the average of the 3 QTc values should be used to determine the subject's eligibility.

• Subject reports any food allergies, celiac disease, or requirements for specific diet (eg, vegan, vegetarian, low fat).

• Acute illness, as judged by the investigator, within 2 weeks of Day 1 of Treatment Period 1.

• Known or suspected intolerance or hypersensitivity to the investigational products, closely related compounds, or any of the stated ingredients.

• History of thyroid disorder that has not been stabilized on thyroid medication or treatment within 3 months of the Screening Visit.

• History of alcohol or other substance abuse within the last year.

• Routine consumption of more than 3 units of caffeine per day or subjects who experience caffeine withdrawal headaches.

• A positive screen for alcohol or drugs of abuse at the Screening Visit.

• Male subjects who consume more than 3 units of alcohol per day. Female subjects who consume more than 2 units of alcohol per day.

• A positive human immunodeficiency virus antibody screen, hepatitis B surface antigen screen, or hepatitis C virus antibody screen.

• Current use of any other medication (including over-the-counter, herbal, or homeopathic preparations) that could affect (improve or worsen) the study evaluations according to the investigator.

• Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing products in any form (eg, gum, patch) within 30 days prior to Day 1 of Treatment Period 1.

• Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to Day 1 of Treatment Period 1.

• Use of another investigational product within 30 days prior to Day 1 of Treatment Period 1 or active enrollment in another drug or vaccine clinical study.

• Substantial changes in eating habits within 30 days prior to Day 1 of Treatment Period 1, as assessed by the investigator.

• Prior screen failure, randomization, participation, or enrollment in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Pharmacology of Miami	Miami	Florida	United States	33014

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01905553
• Other Study ID Numbers: SPD602-113
• First Posted: Jul 23, 2013
• Last Update Posted: Jun 24, 2021
• Last Verified: Jun 1, 2021

Study Results

Participant Flow

Arm/Group Title	SSP-004184SS Fed First	SSP-004184SS Fasted First
Arm/Group Description	Subjects received a single dose SSP-004184SS 21.8mg/kg on Day 1 administered 30 minutes after starting a standard high-fat, high-calorie breakfast in Treatment Period 1. During Treatment Period 2, subjects received a single-dose administration of 21.8mg/kg of SSP-004184SS under fasted conditions.	Subjects received a single-dose administration of 21.8mg/kg of SSP-004184SS under fasted conditions on Day 1 in Treatment Period 1. During Treatment Period 2, subjects received a single dose SSP-004184SS 21.8mg/kg on Day 1 administered 30 minutes after starting a standard high-fat, high-calorie breakfast.
Period Title: Period 1
STARTED	5	4
COMPLETED	5	4
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	5	4
COMPLETED	4	4
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	SSP-004184SS Fed First	SSP-004184SS Fasted First	Total
Arm/Group Description	Subjects received a single dose SSP-004184SS 21.8mg/kg on Day 1 administered 30 minutes after starting a standard high-fat, high-calorie breakfast in Treatment Period 1. During Treatment Period 2, subjects received a single-dose administration of 21.8mg/kg of SSP-004184SS under fasted conditions.	Subjects received a single-dose administration of 21.8mg/kg of SSP-004184SS under fasted conditions on Day 1 in Treatment Period 1. During Treatment Period 2, subjects received a single dose SSP-004184SS 21.8mg/kg on Day 1 administered 30 minutes after starting a standard high-fat, high-calorie breakfast.	Total of all reporting groups
Overall Participants	5	4	9
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	4 100%	9 100%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42 (10.89)	35 (7.62)	38.9 (9.73)
Sex: Female, Male (Count of Participants)
Female	1 20%	2 50%	3 33.3%
Male	4 80%	2 50%	6 66.7%
Region of Enrollment (Count of Participants)
UNITED STATES	5 100%	4 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of SSP-004184 Under Fasted and Fed Conditions
Description	AUCinf is the area under the plasma concentration versus time curve from time 0 to infinity. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Time Frame	Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set: All subjects in the Safety Set for whom the primary pharmacokinetic data were considered sufficient and interpretable.

Arm/Group Title	SSP-004184SS (Fed)	SSP-004184SS (Fasted)
Arm/Group Description	21.8 mg/kg (oral capsule form) given once on Day 1 under fed conditions.	21.8 mg/kg (oral capsule form) given once on Day 1 under fasted conditions.
Measure Participants	9	9
Mean (Standard Deviation) [ng*hr/mL]	112,236.7 (28,804.8)	154,676.6 (28,185.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SSP-004184SS (Fed), SSP-004184SS (Fasted)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The magnitude effect of food on the pharmacokinetic parameters was evaluated by calculating the point estimate and 90% CIs between Treatment A (test treatment, fed) and Treatment B (reference treatment, fasted).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Means
	Estimated Value	0.718
	Confidence Interval	(2-Sided) 90%; 0.670 to 0.770
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of SSP-004184 Under Fed and Fasted Conditions
Description	AUClast is the area under the curve from the time of dosing to the last measurable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.
Time Frame	Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Set: All subjects in the Safety Set for whom the primary pharmacokinetic data were considered sufficient and interpretable.

Arm/Group Title	SSP-004184SS (Fed)	SSP-004184SS (Fasted)
Arm/Group Description	21.8 mg/kg (oral capsule form) given once on Day 1 under fed conditions.	21.8 mg/kg (oral capsule form) given once on Day 1 under fasted conditions.
Measure Participants	9	9
Mean (Standard Deviation) [ng*hr/mL]	112,066.1 (28,822.9)	154,446 (28,066.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SSP-004184SS (Fed), SSP-004184SS (Fasted)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The magnitude effect of food on the pharmacokinetic parameters was evaluated by calculating the point estimate and 90% CIs between Treatment A (test treatment, fed) and Treatment B (reference treatment, fasted).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Means
	Estimated Value	0.718
	Confidence Interval	(2-Sided) 90%; 0.670 to 0.769
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of SSP-004184 Under Fed and Fasted Conditions
Description	Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated.
Time Frame	Study Periods 1 & 2: Within 30 minutes pre-dose, and Post-dose 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24, 48, 72 hours.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SSP-004184SS (Fed)	SSP-004184SS (Fasted)
Arm/Group Description	21.8 mg/kg (oral capsule form) given once on Day 1 under fed conditions.	21.8 mg/kg (oral capsule form) given once on Day 1 under fasted conditions.
Measure Participants	9	9
Mean (Standard Deviation) [ng/mL]	32,755.6 (11,797.4)	70,733.3 (9,782.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SSP-004184SS (Fed), SSP-004184SS (Fasted)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The magnitude effect of food on the pharmacokinetic parameters was evaluated by calculating the point estimate and 90% CIs between Treatment A (test treatment, fed) and Treatment B (reference treatment, fasted).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Geometric LS Means
	Estimated Value	0.449
	Confidence Interval	(2-Sided) 90%; 0.380 to 0.530
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	SSP-004184SS (Fed)		SSP-004184SS (Fasted)
Arm/Group Description	21.8 mg/kg (oral capsule form) given once on Day 1 under fed conditions.		21.8 mg/kg (oral capsule form) given once on Day 1 under fasted conditions.
All Cause Mortality
	SSP-004184SS (Fed)		SSP-004184SS (Fasted)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	SSP-004184SS (Fed)		SSP-004184SS (Fasted)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	SSP-004184SS (Fed)		SSP-004184SS (Fasted)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)		4/9 (44.4%)
Musculoskeletal and connective tissue disorders
Pain in extremity	1/9 (11.1%)	1	0/9 (0%)	0
Nervous system disorders
Headache	2/9 (22.2%)	2	1/9 (11.1%)	1
Psychiatric disorders
Agitation	0/9 (0%)	0	1/9 (11.1%)	2
Renal and urinary disorders
Chromaturia	2/9 (22.2%)	2	2/9 (22.2%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.