Study of SSP-004184 (SPD602) in Healthy Adults and Subjects With Impaired Liver Function
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
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:
|
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:
|
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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.
- 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.
- Total Body Clearance (CL/F) of SSP-004184 [Over 96 hours post-dose]
The rate at which a drug is removed from the body.
- 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
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.- SPD602-105
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
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)
|
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)
|
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
|
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)
|
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)
|
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
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 |
ClinicalTransparency@shire.com |
- SPD602-105