Study of SSP-004184 (SPD602) in Healthy Adults and Subjects With Impaired Liver Function

• ClinicalTrials.gov Identifier: NCT01732263
• Recruitment Status: Completed
• First Posted: November 22, 2012
• Results First Posted: May 15, 2014
• Last Update Posted: May 15, 2014
• Sponsor: Shire
• Information provided by (Responsible Party): Shire

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Hepatic Impairment; Healthy
• Intervention: Drug: SSP-004184
• Enrollment: 44

Participant Flow

Recruitment Details
Pre-assignment Details	One subject withdrew from study prior to randomization (n = 43).

Arm/Group Title	Hepatic Impairment	Matched Healthy Subjects
Arm/Group Description	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).
Period Title: Overall Study
Started	23	20
Completed	23	20
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Hepatic Impairment	Matched Healthy Subjects	Total
Arm/Group Description		All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	Total of all reporting groups
Overall Number of Baseline Participants		23	20	43
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	23 participants	20 participants	43 participants
		56.3 (5.13)	55.1 (5.51)	55.7 (5.28)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	23 participants	20 participants	43 participants
>=65 years		1	0	1
Between 18 and 65 years		22	20	42
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	20 participants	43 participants
	Female	4 17.4%	4 20.0%	8 18.6%
	Male	19 82.6%	16 80.0%	35 81.4%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
UNITED STATES	Number Analyzed	23 participants	20 participants	43 participants
		23	20	43

Outcome Measures

1. Primary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC) of SSP-004184
Description	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 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Analysis Set consists of all enrolled subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.

Arm/Group Title	SSP-004184 (Child-Pugh A Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 45 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh C Liver Impaired) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 50 mg/kg
Arm/Group Description:	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).
Overall Number of Participants Analyzed	8	5	3	7	10	10
Mean (Standard Deviation); Unit of Measure: ng*h/ml
	254327.7 (57645.3)	443053.5 (157352.1)	288579.6 (149123.5)	410414.3 (111201.8)	209989.8 (83155.2)	310281.3 (112004.9)

2. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of SSP-004184
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	Over 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Analysis Set consists of all enrolled subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.

Arm/Group Title	SSP-004184 (Child-Pugh A Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 45 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh C Liver Impaired) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 50 mg/kg
Arm/Group Description:	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).
Overall Number of Participants Analyzed	8	5	3	7	10	10
Mean (Standard Deviation); Unit of Measure: ng/ml
	98887.5 (29689.1)	121460.0 (28777.7)	109166.7 (52920.5)	123985.0 (34807.1)	83350.0 (28538.1)	108890.0 (41016.6)

3. Primary Outcome

Title	Time of Maximum Plasma Concentration (Tmax) for SSP-004184
Description	Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.
Time Frame	Over 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Analysis Set consists of all enrolled subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.

Arm/Group Title	SSP-004184 (Child-Pugh A Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 45 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh C Liver Impaired) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 50 mg/kg
Arm/Group Description:	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).
Overall Number of Participants Analyzed	8	5	3	7	10	10
Median (Full Range); Unit of Measure: hours
	1.3; (1.0 to 1.5)	1.5; (1.0 to 2.5)	1.5; (1.0 to 1.5)	1.5; (1.0 to 2.5)	1.0; (1.0 to 1.5)	1.0; (1.0 to 2.0)

4. Primary Outcome

Title	Plasma Half-Life (T 1/2) of SSP-004184
Description	The time it takes for the blood plasma concentration of a substance to halve.
Time Frame	Over 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Analysis Set consists of all enrolled subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.

Arm/Group Title	SSP-004184 (Child-Pugh A Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 45 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh C Liver Impaired) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 50 mg/kg
Arm/Group Description:	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).
Overall Number of Participants Analyzed	8	5	3	7	10	10
Mean (Standard Deviation); Unit of Measure: hours
	21.91 (17.54)	11.37 (6.47)	6.93 (0.94)	6.79 (3.97)	12.51 (4.51)	16.19 (8.62)

5. Primary Outcome

Title	Total Body Clearance (CL/F) of SSP-004184
Description	The rate at which a drug is removed from the body.
Time Frame	Over 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Analysis Set consists of all enrolled subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.

Arm/Group Title	SSP-004184 (Child-Pugh A Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 45 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh C Liver Impaired) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 50 mg/kg
Arm/Group Description:	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).
Overall Number of Participants Analyzed	8	5	3	7	10	10
Mean (Standard Deviation); Unit of Measure: L/h/kg
	0.204 (0.042)	0.110 (0.035)	0.198 (0.099)	0.119 (0.047)	0.246 (0.097)	0.182 (0.072)

6. Primary Outcome

Title	Volume of Distribution (Vz/F) of SSP-004184
Description	The distribution of a medication between plasma and the rest of the body.
Time Frame	Over 96 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set for whom the primary pharmacokinetic data were considered sufficient and interpretable. Safety Analysis Set consists of all enrolled subjects who took at least 1 dose of investigational product and had at least 1 post-dose safety assessment.

Arm/Group Title	SSP-004184 (Child-Pugh A Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 45 mg/kg	SSP-004184 (Child-Pugh B Liver Impaired) 50 mg/kg	SSP-004184 (Child-Pugh C Liver Impaired) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 45 mg/kg	SSP-004184 (Matched Healthy Subjects) 50 mg/kg
Arm/Group Description:	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	The Child-Pugh Score is a scoring system used to determine the prognosis with cirrhosis and need for liver transplantation. Scoring is based upon albumin, ascites, total bilirubin, prothrombin time, and encephalopathy. Each category is based on a scoring system of 1-3 with 3 being the worst and a total score range of 5-15. It is broken into categories A (score of 5-6), B (score of 7-9), and C (score of 10-15) with worsening from A to C for prognosis. All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).	All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1 (or a revised dose if dose modifications are warranted).
Overall Number of Participants Analyzed	8	5	3	7	10	10
Mean (Standard Deviation); Unit of Measure: L/kg
	6.344 (5.276)	1.796 (1.210)	2.043 (1.259)	1.370 (1.539)	4.103 (1.420)	4.086 (2.237)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Hepatic Impairment		Matched Healthy Subjects
Arm/Group Description	[Not Specified]		[Not Specified]
All-Cause Mortality
	Hepatic Impairment		Matched Healthy Subjects
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Hepatic Impairment		Matched Healthy Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0.00%)		0/20 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Hepatic Impairment		Matched Healthy Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/23 (52.17%)		17/20 (85.00%)
Gastrointestinal disorders
Constipation	1/23 (4.35%)	1	1/20 (5.00%)	1
General disorders
Fatigue	0/23 (0.00%)	0	1/20 (5.00%)	1
Infections and infestations
Nasopharyngitis	0/23 (0.00%)	0	1/20 (5.00%)	1
Nervous system disorders
Headache	2/23 (8.70%)	2	4/20 (20.00%)	4
Psychiatric disorders
Anxiety	0/23 (0.00%)	0	1/20 (5.00%)	1
Renal and urinary disorders
Chromaturia	10/23 (43.48%)	10	17/20 (85.00%)	17

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Study Physician
• Organization: Shire Development LLC
• Phone: +1 866 842 5335

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01732263
• Other Study ID Numbers: SPD602-105
• First Submitted: November 19, 2012
• First Posted: November 22, 2012
• Results First Submitted: April 16, 2014
• Results First Posted: May 15, 2014
• Last Update Posted: May 15, 2014