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

Sponsor
Shire (Industry)
Overall Status
Completed
CT.gov ID
NCT01732263
Collaborator
(none)
44
2
4
4.7
22
4.7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate how much of the study drug SSP-004184 (SPD602) is absorbed by the body and how long it takes to be eliminated from the body in healthy subjects and subjects with mild, moderate, and severe hepatic (liver) impairment compared with subjects with healthy normal liver function.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
44 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-label, Single-dose Study of the Pharmacokinetics, Safety, and Tolerability of SSP-004184 (SPD602) in Subjects With Hepatic Impairment Compared to Matched Healthy Subjects
Actual Study Start Date :
Nov 9, 2012
Actual Primary Completion Date :
Apr 1, 2013
Actual Study Completion Date :
Apr 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: SSP-004184 (Child-Pugh A Liver Impaired)

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.

Drug: SSP-004184
All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1
Other Names:
  • SPD602, FBS0701
  • Experimental: SSP-004184 (Child-Pugh B Liver Impaired)

    Drug: SSP-004184
    All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1
    Other Names:
  • SPD602, FBS0701
  • Experimental: SSP-004184 (Child-Pugh C Liver Impaired)

    Drug: SSP-004184
    All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1
    Other Names:
  • SPD602, FBS0701
  • Experimental: SSP-004184 (Matched Healthy Subjects)

    Drug: SSP-004184
    All subjects will take a single oral dose of SSP-004184 (SPD602) (50 mg/kg) on Day 1
    Other Names:
  • SPD602, FBS0701
  • Outcome Measures

    Primary Outcome Measures

    1. Area Under the Plasma Concentration-time Curve (AUC) of SSP-004184 [Over 96 hours post-dose]

      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 SSP-004184 [Over 96 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 administrated.

    3. Time of Maximum Plasma Concentration (Tmax) for SSP-004184 [Over 96 hours post-dose]

      Tmax is the time after administration of a drug when the maximum plasma concentration in the body is reached.

    4. Plasma Half-Life (T 1/2) of SSP-004184 [Over 96 hours post-dose]

      The time it takes for the blood plasma concentration of a substance to halve.

    5. Total Body Clearance (CL/F) of SSP-004184 [Over 96 hours post-dose]

      The rate at which a drug is removed from the body.

    6. Volume of Distribution (Vz/F) of SSP-004184 [Over 96 hours post-dose]

      The distribution of a medication between plasma and the rest of the body.

    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.

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

    • Male, or

    • Non pregnant, non lactating female

    • Females must be at least 90 days post partum or nulliparous.

    Subjects who do not have hepatic impairment (healthy subjects)

    • Normal renal function.

    Subjects with hepatic impairment

    • Subjects must provide a letter of evaluation from a hepatologist or copy of supporting documents confirming the subject's hepatic impairment (a liver biopsy is preferable but not mandatory).

    • Hepatic impairment should be primary and must not be a complication of an underlying primary systemic disease (eg, patients with metastatic cancer and cancer cachexia)

    • Documented chronic stable liver impairment

    Exclusion Criteria

    Subjects who do not have hepatic impairment (healthy subjects)

    • A positive HIV antibody screen, Hepatitis B surface antigen, or Hepatitis C virus antibody screen.

    Subjects with hepatic impairment

    • Presence of a hepatocellular carcinoma, or an acute hepatic disease caused by an infection or drug toxicity.

    • Presence of surgically created or transjugular intrahepatic portal systemic shunts.

    • A positive HIV antibody screen.

    • Renal insufficiency.

    All subjects

    • Subject has a history of thyroid disorder.

    • History of nephrotic syndrome.

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

    • A positive screen for alcohol or drugs of abuse.

    • Male subjects who consume more than 3 units of alcohol per day. Female subjects who consume more than 2 units of alcohol per day. (1 alcohol unit = 1 beer [12 oz/355 mL] = 1 wine [5 oz/150 mL] = 1 liquor [1.5 oz/40 mL] = 0.75 oz/20 mL alcohol.)

    • Caffeine consumption: For healthy subjects: Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches or have a history of caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6 oz/180 mL cup of coffee, two 12 oz/355 mL (ie, 24 oz/710 mL cola) cans of cola, one 12 oz/355 mL cup of tea, three 1 oz/28 g chocolate bars (ie, 3 oz/85 g chocolate). Decaffeinated coffee, tea, or cola are not considered to contain caffeine.)

    • Donation of blood or blood products within 60 days.

    • Substantial changes in eating habits within 30 days.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clinical Pharmacology of Miami Miami Florida United States 33014
    2 Orlando Clinical Research Center (OCRC) Orlando Florida United States 32809

    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:
    NCT01732263
    Other Study ID Numbers:
    • SPD602-105
    First Posted:
    Nov 22, 2012
    Last Update Posted:
    Jul 19, 2021
    Last Verified:
    Jun 1, 2021
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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 Participants 23 20 43
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    56.3
    (5.13)
    55.1
    (5.51)
    55.7
    (5.28)
    Age, Customized (Count of Participants)
    >=65 years
    1
    4.3%
    0
    0%
    1
    2.3%
    Between 18 and 65 years
    22
    95.7%
    20
    100%
    42
    97.7%
    Sex: Female, Male (Count of Participants)
    Female
    4
    17.4%
    4
    20%
    8
    18.6%
    Male
    19
    82.6%
    16
    80%
    35
    81.4%
    Region of Enrollment (Count of Participants)
    UNITED STATES
    23
    100%
    20
    100%
    43
    100%

    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).
    Measure Participants 8 5 3 7 10 10
    Mean (Standard Deviation) [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).
    Measure Participants 8 5 3 7 10 10
    Mean (Standard Deviation) [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).
    Measure Participants 8 5 3 7 10 10
    Median (Full Range) [hours]
    1.3
    1.5
    1.5
    1.5
    1.0
    1.0
    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).
    Measure Participants 8 5 3 7 10 10
    Mean (Standard Deviation) [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).
    Measure Participants 8 5 3 7 10 10
    Mean (Standard Deviation) [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).
    Measure Participants 8 5 3 7 10 10
    Mean (Standard Deviation) [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
    Adverse Event Reporting Description
    Arm/Group Title Hepatic Impairment Matched Healthy Subjects
    Arm/Group Description
    All Cause Mortality
    Hepatic Impairment Matched Healthy Subjects
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Hepatic Impairment Matched Healthy Subjects
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/23 (0%) 0/20 (0%)
    Other (Not Including Serious) Adverse Events
    Hepatic Impairment Matched Healthy Subjects
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/23 (52.2%) 17/20 (85%)
    Gastrointestinal disorders
    Constipation 1/23 (4.3%) 1 1/20 (5%) 1
    General disorders
    Fatigue 0/23 (0%) 0 1/20 (5%) 1
    Infections and infestations
    Nasopharyngitis 0/23 (0%) 0 1/20 (5%) 1
    Nervous system disorders
    Headache 2/23 (8.7%) 2 4/20 (20%) 4
    Psychiatric disorders
    Anxiety 0/23 (0%) 0 1/20 (5%) 1
    Renal and urinary disorders
    Chromaturia 10/23 (43.5%) 10 17/20 (85%) 17

    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.

    Results Point of Contact

    Name/Title Study Director
    Organization Shire
    Phone +1 866 842 5335
    Email ClinicalTransparency@shire.com
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT01732263
    Other Study ID Numbers:
    • SPD602-105
    First Posted:
    Nov 22, 2012
    Last Update Posted:
    Jul 19, 2021
    Last Verified:
    Jun 1, 2021