A Study of the Safety, Blood Levels and Biological Effects of GBT440 in Healthy Subjects and Subjects With Sickle Cell Disease

Healthy Subjects Clinical Trial

Official title:

A Phase I Randomised, Placebo-controlled, Double-blind, Single and Multiple Ascending Dose Study of the Tolerability and Pharmacokinetics of GBT440 in Healthy Subjects and Patients With Sickle Cell Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02285088
• Other study ID #: GBT440-001
• Secondary ID: 2014-003555-62
• Status: Completed
• Phase: Phase 1
• First received: November 4, 2014
• Last updated: February 13, 2018
• Start date: December 2014
• Est. completion date: May 2017

Study information

• Verified date: February 2018
• Source: Global Blood Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic effects of GBT440 compared with placebo in healthy subjects and subjects with sickle cell disease (SCD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: May 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy male or female of non-child bearing potential; 18 to 55 years old; are non-smokers and have not used nicotine products within 3 months prior to screening.

• Male or female, 18 to 60 years old, with sickle cell disease (hemoglobin SS, HbS/ß0thalassemia, HbS/ß+thalassemia, or HbSC) not requiring chronic blood transfusion therapy; without hospitalization in 30 days before screening or receiving blood transfusion within 30 days before screening; subjects are allowed concomitant use of hydroxyurea if the dose has been stable for the 3 months prior to screening.

Exclusion Criteria:

• Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders.

• Subjects who consume more than 14 (female subjects) or 21 (male subjects) units of alcohol a week.

• Subjects who have used any investigational product in any clinical trial within 30 days of screening

• Subjects with sickle cell disease who smoke >10 cigarettes per day; have hemoglobin level <6 g/dL or >10.4 g/dL (> ULN (appropriately corrected for gender) for Cohort 15) at screening; have aspartate aminotransferase (AST) >4x upper limit of normal or alanine aminotransferase (ALT), or alkaline phosphatase (ALK) >3x upper limit of normal reference range (ULN) at screening; have moderate or severe renal dysfunction

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Healthy Subjects
• Sickle Cell Disease

Intervention

Drug:
• GBT440
GBT440 will be administered as oral capsules
• Placebo
Matching placebo will be administered as oral capsules

Locations

Country	Name	City	State
United Kingdom	Guy's Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Global Blood Therapeutics

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of sickled cells under ex vivo conditions		30 - 90 days
Other	Effect of GBT440 on hemolysis as measured by LDH, direct bilirubin, hemoglobin, and reticulocyte count		30 - 118 days
Other	Change from baseline in pain as measured by visual analog scale		30 days
Other	Change from baseline in fatigue as measured by questionnaire		30 - 118 days
Other	Exercise capacity as measured by 6-minute walk test		30 - 90 days
Primary	Safety, as assessed by frequency and severity of adverse events (AEs), and changes in vital signs, 12-lead electrocardiograms (ECGs), and laboratory assessments as compared to baseline		30 - 118 days
Secondary	Blood and plasma area under the concentration time curve (AUC) of GBT440		30 - 118 days
Secondary	Blood and plasma maximum concentration (Cmax) of GBT440		30 - 118 days
Secondary	Blood and plasma time to maximum concentration (Tmax) of GBT440		30 - 118 days
Secondary	Percentage of hemoglobin occupied or modified by GBT440		30 days
Secondary	Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers		30 days