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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

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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

Tracking Information
First Submitted Date  ICMJE November 4, 2014
First Posted Date  ICMJE November 6, 2014
Last Update Posted Date February 15, 2018
Actual Study Start Date  ICMJE December 2014
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2017)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 4, 2014)
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 days ]
Change History Complete list of historical versions of study NCT02285088 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2017)
  • Blood and plasma area under the concentration time curve (AUC) of GBT440 [ Time Frame: 30 - 118 days ]
  • Blood and plasma maximum concentration (Cmax) of GBT440 [ Time Frame: 30 - 118 days ]
  • Blood and plasma time to maximum concentration (Tmax) of GBT440 [ Time Frame: 30 - 118 days ]
  • Percentage of hemoglobin occupied or modified by GBT440 [ Time Frame: 30 days ]
  • Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers [ Time Frame: 30 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2014)
  • Blood and plasma area under the concentration time curve (AUC) of GBT440 [ Time Frame: 30 days ]
  • Blood and plasma maximum concentration (Cmax) of GBT440 [ Time Frame: 30 days ]
  • Blood and plasma time to maximum concentration (Tmax) of GBT440 [ Time Frame: 30 days ]
  • Percentage of hemoglobin occupied or modified by GBT440 [ Time Frame: 30 days ]
  • Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers [ Time Frame: 30 days ]
Current Other Pre-specified Outcome Measures
 (submitted: March 13, 2017)
  • Percentage of sickled cells under ex vivo conditions [ Time Frame: 30 - 90 days ]
  • Effect of GBT440 on hemolysis as measured by LDH, direct bilirubin, hemoglobin, and reticulocyte count [ Time Frame: 30 - 118 days ]
  • Change from baseline in pain as measured by visual analog scale [ Time Frame: 30 days ]
  • Change from baseline in fatigue as measured by questionnaire [ Time Frame: 30 - 118 days ]
  • Exercise capacity as measured by 6-minute walk test [ Time Frame: 30 - 90 days ]
Original Other Pre-specified Outcome Measures
 (submitted: November 4, 2014)
  • Percentage of sickled cells under ex vivo conditions [ Time Frame: 30 days ]
  • Effect of GBT440 on hemolysis as measured by LDH, direct bilirubin, hemoglobin, and reticulocyte count [ Time Frame: 30 days ]
  • Change from baseline in pain [ Time Frame: 30 days ]
  • Change from baseline in fatigue [ Time Frame: 30 days ]
  • Exercise capacity as measured by 6-minute walk test [ Time Frame: 30 days ]
 
Descriptive Information
Brief Title  ICMJE A Study of the Safety, Blood Levels and Biological Effects of GBT440 in Healthy Subjects and Subjects With Sickle Cell Disease
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Healthy Subjects
  • Sickle Cell Disease
Intervention  ICMJE
  • Drug: GBT440
    GBT440 will be administered as oral capsules
  • Drug: Placebo
    Matching placebo will be administered as oral capsules
Study Arms  ICMJE
  • 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)
    Intervention: Drug: GBT440
  • 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)
    Intervention: Drug: Placebo
Publications * Howard J, Hemmaway CJ, Telfer P, Layton DM, Porter J, Awogbade M, Mant T, Gretler DD, Dufu K, Hutchaleelaha A, Patel M, Siu V, Dixon S, Landsman N, Tonda M, Lehrer-Graiwer J. A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease. Blood. 2019 Apr 25;133(17):1865-1875. doi: 10.1182/blood-2018-08-868893. Epub 2019 Jan 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 13, 2018)
133
Original Estimated Enrollment  ICMJE
 (submitted: November 4, 2014)
128
Actual Study Completion Date  ICMJE May 2017
Actual Primary Completion Date March 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02285088
Other Study ID Numbers  ICMJE GBT440-001
2014-003555-62 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Global Blood Therapeutics
Study Sponsor  ICMJE Global Blood Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Josh Lehrer-Graiwer, MD Global Blood Therapeutics
Principal Investigator: Timothy Mant, FRCP FFPM Guy's Hospital
PRS Account Global Blood Therapeutics
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP