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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02285088
Recruitment Status : Completed
First Posted : November 6, 2014
Last Update Posted : February 15, 2018
Sponsor:
Information provided by (Responsible Party):
Global Blood Therapeutics

Study Description
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Brief 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).

Condition or disease Intervention/treatment Phase
Healthy Subjects Sickle Cell Disease Drug: GBT440 Drug: Placebo Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 133 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : December 2014
Actual Primary Completion Date : March 2017
Actual Study Completion Date : May 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: GBT440
Subjects randomized 6:2 to receive daily oral dosing of GBT440 or placebo for 1 day (single dose) and up to 118 days (multiple dose)
 Drug: GBT440
GBT440 will be administered as oral capsules
Placebo Comparator: Placebo
Subjects randomized 6:2 to receive daily oral dosing of GBT440 or placebo for 1 day (single dose) and up to 118 days (multiple dose)
 Drug: Placebo
Matching placebo will be administered as oral capsules


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: 30 - 118 days ]

Secondary Outcome Measures :
  1. Blood and plasma area under the concentration time curve (AUC) of GBT440 [ Time Frame: 30 - 118 days ]
  2. Blood and plasma maximum concentration (Cmax) of GBT440 [ Time Frame: 30 - 118 days ]
  3. Blood and plasma time to maximum concentration (Tmax) of GBT440 [ Time Frame: 30 - 118 days ]
  4. Percentage of hemoglobin occupied or modified by GBT440 [ Time Frame: 30 days ]
  5. Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers [ Time Frame: 30 days ]

Other Outcome Measures:
  1. Percentage of sickled cells under ex vivo conditions [ Time Frame: 30 - 90 days ]
  2. Effect of GBT440 on hemolysis as measured by LDH, direct bilirubin, hemoglobin, and reticulocyte count [ Time Frame: 30 - 118 days ]
  3. Change from baseline in pain as measured by visual analog scale [ Time Frame: 30 days ]
  4. Change from baseline in fatigue as measured by questionnaire [ Time Frame: 30 - 118 days ]
  5. Exercise capacity as measured by 6-minute walk test [ Time Frame: 30 - 90 days ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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/β0thalassemia, HbS/β+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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02285088


Locations
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United Kingdom
Guy's Hospital
London, United Kingdom, SE1 9RT
Sponsors and Collaborators
Global Blood Therapeutics
Investigators
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Study Director: Josh Lehrer-Graiwer, MD Global Blood Therapeutics
Principal Investigator: Timothy Mant, FRCP FFPM Guy's Hospital
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Global Blood Therapeutics
ClinicalTrials.gov Identifier: NCT02285088    
Other Study ID Numbers: GBT440-001
2014-003555-62 ( EudraCT Number )
First Posted: November 6, 2014    Key Record Dates
Last Update Posted: February 15, 2018
Last Verified: February 2018
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
 Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn