Study to Investigate Safety, Tolerability, Pharmacokinetics and Cardiac Function After Repeat Doses of SB-649868 in Healthy-volunteers

NCT01030939 | Completed Phase 1 DMC

• 1 other identifier: 112861
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether SB-649868 is safe, tolerable after repeated administrations in adult and elderly healthy volunteers. Pharmacokinetics and effects on cardiac function of repeated doses are studied

Conditions

Sleep Disorders

Keywords

Healthy volunteers; Men and women; adults and elderly; repeat dose

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability evaluated by adverse event monitoring, ECG, vital signs, physical examination, laboratory values (including cTpn I and Insulin) and Romberg/heel to toe test

  screening period of 28 days followed by 28 days plus a follow up during 2 weeks approximately

Secondary Outcomes (1)

• pharmacokinetic after repeat dose. Pharmacodynamic outcomes:Doppler evaluation for tissue velocities, Doppler evaluation of flow, End diastolic and systolic volume and ejection fraction, E/E', and HOMA

  within 28 days

Study Arms (4)

Cohort 1: SB-649868

EXPERIMENTAL

Healthy adult male subjects

Drug: SB-649868

Cohort 2

EXPERIMENTAL

Healthy adult female subjects

Drug: SB-649868

Cohort 3

EXPERIMENTAL

Healthy male elderly subjects

Drug: SB-649868

Cohort 4

EXPERIMENTAL

Healthy female elderly subjects

Drug: SB-649868

Interventions

SB-649868 DRUG

In each of all cohorts, 18 subjects will be randomised in a 2:1 ratio to receive either SB-649868 or placebo

Cohort 1: SB-649868; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or female subject as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. However,
• Subjects with cTpn I values above 99th percentile of normal range of the selected assay should always be excluded from enrollment;
• Subjects with AST or ALT \> 2xULN should always be excluded from enrollment;
• Subjects with alkaline phosphatase or bilirubin \> 1.5xULN should always be excluded (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Age \> or equal to 18 years (applied only to Cohort 1 and 2); age \>65 years (applied only to Cohort 3 and 4);
• Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 3 days post last dose (equivalent to 5 terminal half-lives post-last dose).
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/mL and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their Hormone Replacement Therapy (HRT) during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of contraceptive methods
• Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception for 6 weeks following discontinuation of study medication.
• Having given written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Average QTcB or QTcF \< 450 msec; PQ 120-220ms; QRS \<120ms; no significant rhythm disorders in SCR 24h Holter-ECG

You may not qualify if:

• History or presence of significant psychiatric, neurological, respiratory, gastrointestinal, hepatic, pancreatic or renal diseases or of any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• History of cardiovascular diseases and/or evidence of repolarization defects
• History of regular alcohol consumption within 6 months of the study defined as:
• an average weekly intake of greater than 21 units (14 units for female) or an average daily intake of greater than 3 units (2 units for female). 1 unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• Vulnerable subjects , or subject is mentally or legally incapacitated, or language barrier precluding adequate understanding of cooperation.
• Any history of suicidal behaviour or any suicidal ideation of type 4 or 5 in the last month on the C-SSRS administered at screening
• Pregnant females as determined by positive Serum beta-hCG test at screening or prior to dosing.
• Lactating females.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• A positive test for HIV antibody.
• cTpn I values above of 99th percentile of the laboratory reference interval
• A positive pre-study drug/alcohol screen.
• Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Berlin, 14050, Germany

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study 112861 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Sleep Wake Disorders; Multiple Endocrine Neoplasia Type 1

Interventions

N-((1-((5-(4-fluorophenyl)-2-methyl-4-thiazolyl)carbonyl)-2-piperidinyl)methyl)-4-benzofurancarboxamide

Condition Hierarchy (Ancestors)

Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2009
• First Posted: December 14, 2009
• Study Start: August 27, 2009
• Primary Completion: January 6, 2010
• Study Completion: January 6, 2010
• Last Updated: June 20, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)