Firategrast (SB683699) Surface Area Study in Multiple Sclerosis Patients

NCT00548769 | Completed Phase 1

• 1 other identifier: A4M109079
• Study Type: interventional
• Target: 37
• Locations: 3 countries
• Sites: 4

Brief Summary

Sufficient subjects with a confirmed diagnosis of MS (EDSS score of 6.5 or below), will be recruited to ensure that 30 subjects (approx. equal numbers of each gender) complete the study. Subjects will undergo a screening visit, then four study days, each separated by a washout period of at least 7 days, when the different firategrast batches of drug substance will be administered, and a follow-up visit.

Conditions

Multiple Sclerosis

Keywords

PK,; SB-683699,; multiple sclerosis; firategrast,; surface area,

Outcome Measures

Primary Outcomes (1)

• The AUC(0-24) for firategrast following administration of tablets made from three different batches of drug with different surface areas.

  Pre-dose. 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post dose

Secondary Outcomes (3)

• Cmax and Tmax. The AUC(0-24) Cmax and Tmax of of SB683699 metabolite GW786375X.

  Pre-dose. 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post dose

• AEs, vital signs and clinical laboratory data during the course of the study.

  Throughout the course of the study

• SB-683699 and GW786375X plasma concentration to derive pharmacokinetic parameters.

  Pre-dose. 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours post dose

Study Arms (4)

Sequence ADBC

EXPERIMENTAL

Subjects will be administered formulation A, formulation D, formulation B and formulation C across four study days each separated by a washout period of at least seven days. Subjects will fast overnight prior to dosing. Blood samples will be collected at intervals over a period of 24 hours post-dose.

Drug: Formulation A; Drug: Formulation B; Drug: Formulation C; Drug: Formulation D

Sequence BACD

EXPERIMENTAL

Subjects will be administered formulation B, formulation A, formulation C and formulation D across four study days each separated by a washout period of at least seven days. Subjects will fast overnight prior to dosing. Blood samples will be collected at intervals over a period of 24 hours post-dose.

Drug: Formulation A; Drug: Formulation B; Drug: Formulation C; Drug: Formulation D

Sequence CBDA

EXPERIMENTAL

Subjects will be administered formulation C, formulation B, formulation D and formulation A across four study days each separated by a washout period of at least seven days. Subjects will fast overnight prior to dosing. Blood samples will be collected at intervals over a period of 24 hours post-dose.

Drug: Formulation A; Drug: Formulation B; Drug: Formulation C; Drug: Formulation D

Sequence DCAB

EXPERIMENTAL

Subjects will be administered formulation D, formulation C, formulation A and formulation B across four study days each separated by a washout period of at least seven days. Subjects will fast overnight prior to dosing. Blood samples will be collected at intervals over a period of 24 hours post-dose.

Drug: Formulation A; Drug: Formulation B; Drug: Formulation C; Drug: Formulation D

Interventions

Formulation A DRUG

Formulation A will contain firategrast drug substance from native drug batch Irvine. Subjects will be administered three tablets of 300 milligrams with drug substance surface area of 2.1 square meter per gram. The tablets will be administered with 240 milliliters of water.

Also known as: firategrast (SB683699)

Sequence ADBC; Sequence BACD; Sequence CBDA; Sequence DCAB

Formulation B DRUG

Formulation B will contain firategrast drug substance from native drug batch Tonbridge. Subjects will be administered three tablets of 300 milligrams with drug substance surface area of 2.6 square meter per gram. The tablets will be administered with 240 milliliters of water.

Sequence ADBC; Sequence BACD; Sequence CBDA; Sequence DCAB

Formulation C DRUG

Formulation C will contain firategrast drug substance from Tonbridge single pass micronized drug. Subjects will be administered three tablets of 300 milligrams with drug substance surface area of 3-4 square meter per gram. The tablets will be administered with 240 milliliters of water.

Sequence ADBC; Sequence BACD; Sequence CBDA; Sequence DCAB

Formulation D DRUG

Formulation D will contain firategrast drug substance from Tonbridge with reduced tablet size. Subjects will be administered three tablets of 300 milligrams with drug substance surface area of 2.6 square meter per gram. The tablets will be administered with 240 milliliters of water.

Sequence ADBC; Sequence BACD; Sequence CBDA; Sequence DCAB

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects aged 18-65 years inclusive with a diagnosis of MS
• EDSS between 0-6.5 inclusive at the Screening visit
• QTc \<450msec
• A female subject is eligible to enter the study if she is of non-childbearing potential, or of childbearing potential, has a negative urine pregnancy test at Screening, and agrees to consistent and correct use of adequate contraception
• Provide a signed and dated written informed consent prior to study participation
• The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
• A negative urine drugs of abuse test.
• No evidence of pulmonary tuberculosis as verified by a negative chest X-ray within the past 6 months

You may not qualify if:

• Subjects receiving corticosteroids within 4 weeks of Screening for treatment of MS. If non-systemic steroids are being used for other chronic inflammatory conditions, subjects may be included at the discretion of the investigator after discussion with the GSK medical monitor.
• Use of an β-interferon product, glatiramer acetate or azathioprine within 3 months of Screening, or use of Mitoxantrone within 12 months of Screening. Subjects who have received other therapies affecting the immune system (such as IVIg, cyclophosphamide, plasmapheresis, or any other immunosuppressive or immunomodulatory treatment) in the past may be included on a case by case basis after discussion with the GSK medical monitor. None of these treatments will be allowed during this study
• Previous exposure to alemtuzumab, natalizumab or bone marrow transplantation or whole body irradiation.
• Subjects with a cardiac pacemaker or any other type of metal implant or with any other contraindication for MRI (including known allergy to gadolinium).
• Use of 4-aminopyridine, rosiglitazone, pioglitazone and any other compounds metabolised primarily through cytochrome P450 2C8 are prohibited at Screening and throughout the study
• Subjects with clinically significant renal laboratory values: subjects with a calculated creatinine clearance \<60ml/min
• Subjects with local urinalysis findings outside of ranges defined in the protocol during the screening period.
• Presence of clinically significant hepatic laboratory values
• CD4 count \<500 cells/µl, CD4:CD8 \<1.0, idiopathic CD4/CD8 lymphopenia or secondary lymphopenia at Screening.
• JCV DNA detected in plasma or buffy coat using PCR
• Any findings on the MRI of the brain other than MS, except for benign findings that require no further evaluation or treatment and do not have an impact on the patient's neurological health
• Current or history of cancer, excluding localized non-melanoma skin cancer.
• Uncontrolled or any active bacterial, viral, or fungal infection. Any previous serious infections should be discussed with the GSK medical monitor (e.g. opportunistic or atypical infections).
• History of tuberculosis or positive chest X-ray for TB
• Known congenital or acquired immunodeficiency.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Prague, 150 18, Czechia

Location

GSK Investigational Site

Berlin, 10117, Germany

Location

GSK Investigational Site

Grodzisk Mazowiecki, 05-825, Poland

Location

GSK Investigational Site

Poznan, 60-479, Poland

Location

Related Links

• Results for study 109079 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Firategrast; D-Worm

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2007
• First Posted: October 24, 2007
• Study Start: April 21, 2007
• Primary Completion: November 26, 2007
• Study Completion: November 26, 2007
• Last Updated: August 1, 2017

Record last verified: 2017-07

Locations

CZ (1); DE (1); PL (2)