Adsorption, Metabolism and Excretion (AME) of Single Dose Radiolabeled SPD557 in Volunteers

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01786876
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 1.2
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief Summary

Phase I study to evaluate the excretion of radioactivity, the metabolic profile, pharmacokinetics, safety and tolerability following a single oral administration of [14C] SPD557 in healthy male volunteers aged 18 to 50 years (inclusive).The purpose of this study is to investigate how and how quickly SPD557 or its break down products are excreted by analysing blood, faeces and urine samples collected during the study.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Radiolabeled SPD557	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase 1 Study to Investigate the Absorption, Metabolism and Excretion of [14C]SPD557 Following a Single Oral Dose in Healthy Male Subjects
• Actual Study Start Date: Mar 7, 2013
• Actual Primary Completion Date: Apr 12, 2013
• Actual Study Completion Date: Apr 12, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Radiolabeled SPD557	Drug: Radiolabeled SPD557; A single oral dose of 2 mg radiolabeled SPD557 administered on Day 1

Outcome Measures

Primary Outcome Measures

1. Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC 0→∞) of Radiolabelled SSP-002358 [Over 240 hours post-dose]

   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. Maximum Plasma Concentration (Cmax) of Radiolabelled SSP-002358 [Over 240 hours post-dose]

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

3. Time to Maximum Plasma Concentration (Tmax) of Radiolabelled SSP-002358 [Over 240 hours post-dose]

4. Plasma Half-Life (T1/2) of Radiolabelled SSP-002358 [Over 240 hours post-dose]

5. AUC 0→∞ Whole Blood Total Radioactivity of Radiolabelled SSP-002358 [Over 240 hours post-dose]

6. Cmax Whole Blood Total Radioactivity of Radiolabelled SSP-002358 [Over 240 hours post-dose]

7. Tmax Whole Blood Total Radioactivity of Radiolabelled SSP-002358 [Over 240 hours post-dose]

8. Half-Life Whole Blood Total Radioactivity of Radiolabelled SSP-002358 [Over 240 hours post-dose]

9. AUC 0→∞ Plasma Total Radioactivity of Radiolabelled SSP-002358 [Over 240 hours post-dose]

10. Cmax Plasma Total Radioactivity of Radiolabelled SSP-002358 [Over 240 hours post-dose]

11. Tmax Plasma Total Radioactivity of Radiolabelled SSP-002358 [Over 240 hours post-dose]

12. Half-Life Plasma Total Radioactivity of Radiolabelled SSP-002358 [Over 240 hours post-dose]

13. Percent Total Radioactivity Excreted in Urine of Radiolabelled SSP-002358 [Over 240 hours post-dose]

14. Percent Total Radioactivity Excreted in Stool of Radiolabelled SSP-002358 [Over 240 hours post-dose]

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Males ages 18 to 50 years

• Have a body mass index (BMI) of ≥18.5 and ≤30 kg/m2

• Subject is willing to comply with any applicable contraceptive and sperm donation requirements

Key Exclusion criteria:

• Have participated in a [14C]-study within the last 6 months.

• Exposure to clinically significant radiation within 12 months prior to dose (for example, serial X-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring).

• Male subjects who consume more than 21 units of alcohol per week or 3 units per day.

• Subjects who report typically having more than 2 bowel movements per day, less than 3 bowel movements per week or those whose bowel habits have changed significantly within 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance	Madison	Wisconsin	United States	53704

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: NCT01786876
• Other Study ID Numbers: SPD557-107
• First Posted: Feb 8, 2013
• Last Update Posted: Jun 10, 2021
• Last Verified: May 1, 2021

• Keywords provided by Shire: Radiolabelled; AME

Study Results

Participant Flow

Arm/Group Title	Radiolabelled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Radiolabelled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 100%
>=65 years	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	29.5 (2.07)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%
Region of Enrollment (Count of Participants)
UNITED STATES	6 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC 0→∞) of Radiolabelled SSP-002358
Description	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	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [pg*h/ml]	43476 (13801)

2. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of Radiolabelled SSP-002358
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 administered.
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [pg/ml]	4643 (894)

3. Primary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Median (Full Range) [hours]	1.25 (1.17)

4. Primary Outcome

Title	Plasma Half-Life (T1/2) of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	5
Mean (Standard Deviation) [hours]	11.0 (2.38)

5. Primary Outcome

Title	AUC 0→∞ Whole Blood Total Radioactivity of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [pg equivalents*h/ml]	101960 (41581)

6. Primary Outcome

Title	Cmax Whole Blood Total Radioactivity of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [pg equivalents/ml]	9252 (2138)

7. Primary Outcome

Title	Tmax Whole Blood Total Radioactivity of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Median (Full Range) [hours]	2.00

8. Primary Outcome

Title	Half-Life Whole Blood Total Radioactivity of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [hours]	6.96 (1.51)

9. Primary Outcome

Title	AUC 0→∞ Plasma Total Radioactivity of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [pg equivalents*h/ml]	137314 (56101)

10. Primary Outcome

Title	Cmax Plasma Total Radioactivity of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [pg equivalents/ml]	11658 (3538)

11. Primary Outcome

Title	Tmax Plasma Total Radioactivity of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Median (Full Range) [hours]	1.50

12. Primary Outcome

Title	Half-Life Plasma Total Radioactivity of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [hours]	10.9 (2.54)

13. Primary Outcome

Title	Percent Total Radioactivity Excreted in Urine of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [percentage of radioactivity]	38.2 (10.3)

14. Primary Outcome

Title	Percent Total Radioactivity Excreted in Stool of Radiolabelled SSP-002358
Time Frame	Over 240 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Set included all subjects with at least 1 PK parameter estimated adequately in the Pharmacokinetic Concentration Analysis Set. Pharmacokinetic Concentration Analysis Set included all subjects who took at least 1 dose of investigational product and underwent plasma PK sampling and had evaluable PK assay results.

Arm/Group Title	Radiolabeled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
Measure Participants	6
Mean (Standard Deviation) [percentage of radioactivity]	57.3 (10.4)

Adverse Events

Arm/Group Title	Radiolabelled SSP-002358
Arm/Group Description	A single oral dose of 2 mg radiolabeled SSP-002358 administered on Day 1
All Cause Mortality
	Radiolabelled SSP-002358
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Radiolabelled SSP-002358
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	Radiolabelled SSP-002358
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Gastrointestinal disorders
Diarrhoea	5/6 (83.3%)	7
Injury, poisoning and procedural complications
Scratch	1/6 (16.7%)	1

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.