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A Study to Compare the Pharmacokinetics of Mepolizumab as a Liquid Drug in a Safety Syringe or an Autoinjector Versus Lyophilised Drug

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ClinicalTrials.gov Identifier: NCT03014674
Recruitment Status : Completed
First Posted : January 9, 2017
Results First Posted : August 14, 2018
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE December 15, 2016
First Posted Date  ICMJE January 9, 2017
Results First Submitted Date  ICMJE July 17, 2018
Results First Posted Date  ICMJE August 14, 2018
Last Update Posted Date December 3, 2019
Actual Study Start Date  ICMJE January 6, 2017
Actual Primary Completion Date August 11, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
  • Maximum Observed Plasma Concentration (Cmax) of Mepolizumab [ Time Frame: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples were collected at indicated time points. Cmax following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with reconstituted lyophilized drug product from the vial. Pharmacokinetic (PK) Population comprised of all participants receiving study drug for whom a pharmacokinetic sample was obtained and analyzed.
  • Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]), AUC From Time Zero Extrapolated to Infinite Time (AUC[0-inf]) of Mepolizumab [ Time Frame: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples were collected at indicated time points. AUC(0-t) and AUC(0-inf) following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Fixed effects analysis of covariance model was used for analysis. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).
Original Primary Outcome Measures  ICMJE
 (submitted: January 6, 2017)
  • Maximum observed plasma concentration (Cmax) following a single dose administration of liquid mepolizumab [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating Cmax. Cmax following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector will be compared with lyophilized drug product.
  • Area under the plasma concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0-t]) following a single dose administration of liquid mepolizumab [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC [0-t]. AUC [0-t] following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector will be compared with lyophilized drug product.
  • Area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-infinity]) following a single dose administration of liquid mepolizumab [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating AUC [0-infinity]. AUC [0-infinity] following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector will be compared with lyophilized drug product.
Change History Complete list of historical versions of study NCT03014674 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
  • Time to Cmax (Tmax) and Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) of Mepolizumab [ Time Frame: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples were collected at indicated time points. Tmax and tlast following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product.
  • Apparent Clearance (CL/F) of Mepolizumab [ Time Frame: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples were collected at indicated time points . CL/F following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.
  • Apparent Volume of Distribution (Vd/F) of Mepolizumab [ Time Frame: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples were collected at indicated time points. Vd/F following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.
  • Terminal Phase Elimination Rate Constant (Lambda z) of Mepolizumab [ Time Frame: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples were collected at indicated time points. Lambda z following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.
  • Terminal Phase Half-life (t½) of Mepolizumab [ Time Frame: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples were collected at indicated time points for calculating t½. t½ following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.
  • Percentage of AUC(0-inf) Obtained by Extrapolation (% AUCex) of Mepolizumab [ Time Frame: Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples were collected at indicated time points. Percentage AUCex following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Only those participants with data available were analyzed.
  • Number of Participants With On-treatment Non-serious Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: Up to 28 days post-dose ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All Treated Subjects (Safety) comprised of all participants who received mepolizumab. Participants with non-serious AEs (3 percentage threshold) and SAEs has been reported.
  • Number of Participants With On-treatment Systemic Reactions and Injection Site Reactions [ Time Frame: Up to 28 days post-dose ]
    Adverse events of special interest like local injection site reactions and systemic reactions like allergic Type I hypersensitivity were reported along with AEs and SAEs. Participants with local injection site reaction and Allergic Type I hypersensitivity systemic reactions are reported here.
  • Number of Participants With Hematology Parameters Shifts From Baseline Relative to Normal Range [ Time Frame: Up to Day 85 ]
    Hematology parameters included assessment of platelet count, erythrocytes, leukocytes, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin and hematocrit. Participants were counted in the worst case category that their value changes to Low, Normal or High. Participants whose value category was unchanged or whose value became normal, were recorded in the "To Normal or No Change" category. The worst case post-Baseline values has been reported. For basophils the "to low" category is not applicable (NA) as the lower limit of normal is zero for this parameter.
  • Number of Participants With Clinical Chemistry Parameters Shifts From Baseline Relative to Normal Range [ Time Frame: Up to Day 85 ]
    Blood samples were collected to evaluate clinical chemistry parameters, which included assessment of creatinine, creatine kinase, glucose, protein, potassium, urea, sodium, calcium, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin (D.bili) and bilirubin, and albumin. Participants were counted in the worst case category that their value changes to Low, Normal or High. Participants whose value category was unchanged or whose value became normal, were recorded in the "To Normal or No Change" category. The worst case post-Baseline values has been reported. Only those participants with data available at the specified data points were analyzed. For the category "to low " NA indicates data was not available as the lower limit of normal is zero for this parameter.
  • Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) [ Time Frame: Baseline and up to Day 85 ]
    SBP and DBP were measured in supine position after 5 minutes rest. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
  • Change From Baseline in Pulse Rate [ Time Frame: Baseline and up to Day 85 ]
    Pulse rate was measured in supine position after 5 minutes rest. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
  • Change From Baseline in Temperature [ Time Frame: Baseline and up to Day 85 ]
    Temperature was measured in supine position after 5 minutes rest. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
  • Change From Baseline in Respiratory Rate [ Time Frame: Baseline and up to Day 85 ]
    Respiratory rate was measured in supine position after 5 minutes rest. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
  • Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings [ Time Frame: Baseline and Day 85 ]
    Single measurements of 12-lead ECGs were obtained after 5 minutes of rest in a supine position for the participant. ECG was performed on Day 1 and Day 85 using an automated ECG machine. Baseline values for each assessment was the latest available assessment prior to receiving the single dose of mepolizumab. Change from Baseline was defined as difference between the post-Baseline visit value and the Baseline value. Participants with abnormal ECG findings that are clinically not significant and clinically significant data has been presented here. The data of worst case post-Baseline is presented here. Only those participants available at the specified time points were analyzed.
  • Number of Participants With Positive Anti-mepolizumab Binding Antibodies [ Time Frame: Up to Day 85 ]
    Blood samples were collected for the determination of anti-mepolizumab antibodies. A binding anti-drug antibody (ADA) assay was performed. There were three tiered analysis: screening, confirmation and titration. The results of binding ADA were categorized as negative, transient positive (defined as a single confirmatory positive immunogenic response that does not occur at the final study assessment) or persistent positive (defined as a confirmatory positive immunogenic response for at least 2 consecutive assessments excluding the Screening visit, or a single result at the final study assessment). A participant was considered positive if they had at least one positive post-Baseline ADA result. Number of participants with positive anti-mepolizumab antibodies at any time post-Baseline are presented here. Only those participants available at the specified time points were analyzed.
  • Number of Participants With Positive Neutralizing Antibodies [ Time Frame: Up to Day 85 ]
    Blood samples were collected for the determination of positive neutralizing antibodies. A neutralizing antibody assay was performed. Neutralizing antibody test was only carried out for participants who have had a positive confirmatory binding antibody test result at visit. A participant was considered positive if they had at least one positive post-Baseline neutralizing antibody result. Number of participants with positive neutralizing antibodies at any time post-Baseline are presented here. Only those participants available at the specified time points were analyzed.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2017)
  • Apparent clearance (CL/F) following a single dose administration of liquid mepolizumab [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating CL/F. Parameter following a single dose administration of liquid mepolizumab using an autoinjector or a safety syringe will be compared with the lyophilized drug product.
  • Apparent volume of distribution (Vd/F) following a single dose administration of liquid mepolizumab [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating Vd/F. Parameter following a single dose administration of liquid mepolizumab using an autoinjector or a safety syringe will be compared with the lyophilized drug product.
  • Volume of distribution (Vz) following a single dose administration of liquid mepolizumab [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating Vz. Parameter following a single dose administration of liquid mepolizumab using an autoinjector or a safety syringe will be compared with the lyophilized drug product.
  • Terminal phase rate constant (λz) following a single dose administration of liquid mepolizumab [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating λz. Parameter following a single dose administration of liquid Mepolizumab using an autoinjector or a safety syringe will be compared with the lyophilized drug product.
  • Area under the plasma concentration-time curve extrapolated from time t to infinity as a percentage of total AUC (%AUCex) following a single dose administration of liquid mepolizumab [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating %AUCex. Parameter following a single dose administration of liquid mepolizumab using an autoinjector or a safety syringe will be compared with the lyophilized drug product.
  • Number of subjects with adverse event (AE) and serious adverse event (SAE) including systemic reactions and injection site reactions. [ Time Frame: Up to Day 85 ]
    AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE.
  • Number of subjects with abnormal clinical laboratory parameters [ Time Frame: Up to Day 85 ]
    Blood samples will be collected to analyze aspartate aminotransferase (AST), alkaline Phosphatase (ALP), alanine aminotransferase (ALT), creatinine, blood urea nitrogen, creatine kinase, total bilirubin, direct bilirubin, total protein, albumin, glucose, sodium, potassium, calcium
  • Number of subjects with abnormal hematology laboratory parameters [ Time Frame: Up to Day 85 ]
    Blood samples will be collected to analyze White Blood Cells (WBC), neutrophils, basophils, eosinophils, lymphocytes, monocytes, Red Blood Cells (RBC) count, RBC indices, average red blood cell size (MCV), hemoglobin amount per red blood cell (MCH) hemoglobin, hematocrit, and platelet count
  • Blood pressure assessment as a measure of safety [ Time Frame: Up to Day 85 ]
    Systolic and diastolic blood pressure will be measured in a supine position at Day 1 (pre-dose), Days 2, 3, 4, 5, 6, 7, 43 and 85 post-dose
  • Measurement of pulse rate as a measure of safety [ Time Frame: Up to Day 85 ]
    Pulse rate will be measured in a supine position at Day 1 (pre-dose), Days 2, 3, 4, 5, 6, 7, 43 and 85 post-dose
  • Body temperature assessment as a measure of safety [ Time Frame: Up to Day 85 ]
    Temperature will be measured in a supine position at Day 1 (pre-dose), Days 2, 3, 4, 5, 6, 7, 43 and 85 post-dose
  • Measurement of respiratory rate as a safety measure [ Time Frame: Up to Day 85 ]
    Respiratory rate will be measured in a supine position at Day 1 (pre-dose), Days 2, 3, 4, 5, 6, 7, 43 and 85 post-dose
  • Electrocardiogram (ECG) as a measure of safety [ Time Frame: Up to Day 85 ]
    Single 12-lead ECG will be obtained in supine position after 5 minutes rest
  • Frequency of positive anti mepolizumab binding antibodies and neutralizing antibodies following a single dose administration of liquid mepolizumab [ Time Frame: Up to Day 85 ]
    Blood samples will be collected Day 1 (pre-dose), Days 29, 43, and 85 post-dose for determination of anti-mepolizumab antibodies
  • Time to maximum observed plasma drug concentration (tmax) [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating tmax. Parameters following a single dose administration of liquid mepolizumab using an autoinjector or a safety syringe will be compared with the lyophilized drug product.
  • Terminal elimination half-life (t1/2) of mepolizumab [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating t1/2. Parameters following a single dose administration of liquid mepolizumab using an autoinjector or a safety syringe will be compared with the lyophilized drug product.
  • Time to last measurable concentration (tlast) [ Time Frame: Pre-dose, 2hours (h), 8h, 24h (Day 2), 48h (Day 3) and on Days 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose ]
    Blood samples will be collected at pre-dose and at specific post dose time points for calculating tlast. Parameters following a single dose administration of liquid mepolizumab using an autoinjector or a safety syringe will be compared with the lyophilized drug product.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Compare the Pharmacokinetics of Mepolizumab as a Liquid Drug in a Safety Syringe or an Autoinjector Versus Lyophilised Drug
Official Title  ICMJE An Open Label, Randomised, Three Arm, Single Dose, Multicentre, Parallel Group Study in Healthy Subjects to Compare the Pharmacokinetics of Subcutaneous Mepolizumab When Delivered as a Liquid Drug Product in a Safety Syringe or an Auto Injector With a Reconstituted Lyophilised Drug Product From a Vial
Brief Summary Mepolizumab (SB-240563) is a humanized monoclonal antibody (Immunoglobulin G1, kappa, mAb) that blocks human interleukin-5 (hIL-5) from binding to the interleukin (IL)-5 receptor complex expressed on the eosinophil cell surface and thus inhibits signaling. This study will compare the pharmacokinetics and safety of mepolizumab administered as a liquid drug product in two different devices with the reconstituted lyophilized drug product in healthy subjects. Subjects will receive a single administration of 100 milligram (mg) mepolizumab as a single injection. The randomization will be stratified by body weight (<70 kilogram (kg), 70 <80 kg and >=80 kg) and the site of injection will be randomized 1:1:1 to the upper arm, abdomen or thigh. Approximately 243 healthy subjects will be randomized so that at least 9 subjects are randomized to each mepolizumab treatment within each weight strata and 3 subjects within each mepolizumab treatment, weight strata and injection site. Each subject will participate in the study for up to approximately 16 weeks (up to 85 days after drug administration), and will have a screening visit, a single dose treatment period, and a follow-up visit.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Biological: Lyophilized mepolizumab
    Mepolizumab will be provided as white, uniform, lyophilized cake in vials with unit dose strength of 100 mg/vial for reconstitution in 1.2 mL sterile water for injection (SWFI). Following reconstitution it forms a clear to opalescent, colorless to pale yellow solution for SC injection.
  • Biological: Liquid mepolizumab
    Mepolizumab will be provided as a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled autoinjector or safety syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose ethylenediaminetetraacetic acid and polysorbate 80.
  • Device: Prefilled autoinjector
    Single use, disposable autoinjector will be assembled with the prefilled syringe containing the drug product. It will enable automatic delivery of the drug product under the power of a spring mechanism following activation of the device. Start and end of injection clicks will inform the user of correct use. A plastic needle will cover shield the needle before and after injection to minimize the potential for needle stick injuries.
  • Device: Prefilled Safety Syringe
    Single use, disposable safety syringe with a retracting needle guard and locking system.
Study Arms  ICMJE
  • Experimental: Liquid mepolizumab in safety syringe
    Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled syringe within a safety syringe according to randomization.
    Interventions:
    • Biological: Liquid mepolizumab
    • Device: Prefilled Safety Syringe
  • Experimental: Liquid mepolizumab in an autoinjector
    Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled autoinjector, according to randomization.
    Interventions:
    • Biological: Liquid mepolizumab
    • Device: Prefilled autoinjector
  • Active Comparator: Lyophilised mepolizumab from vial
    Subjects will receive a single dose of 100 mg reconstituted lyophilized mepolizumab manually administered subcutaneously according to randomization
    Intervention: Biological: Lyophilized mepolizumab
Publications * Shabbir S, Pouliquen IJ, Bentley JH, Bradford ES, C Kaisermann M, Albayaty M. The Pharmacokinetics and Relative Bioavailability of Mepolizumab 100 mg Liquid Formulation Administered Subcutaneously to Healthy Participants: A Randomized Trial. Clin Pharmacol Drug Dev. 2019 Jul 17. doi: 10.1002/cpdd.726. [Epub ahead of print]

*   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: October 4, 2017)
246
Original Estimated Enrollment  ICMJE
 (submitted: January 6, 2017)
243
Actual Study Completion Date  ICMJE August 11, 2017
Actual Primary Completion Date August 11, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • 18 years of age and over at the time of signing the informed consent.
  • Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures or ability to interpret study results.
  • Body weight >=50 kg and body mass index (BMI) within the range 19.0-30 kg/square meter(m^2) (inclusive)
  • Male or Female: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: pre-menopausal females with documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up; confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy; post- menopausal females. Subject is of reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 16 weeks after the administration of the single dose of study medication.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol. The subject must be able to understand and communicate in the native language of the site, e.g. German in German sites.

Exclusion Criteria

  • Alanine transaminase >1.5x upper limit of normal (ULN)
  • Bilirubin >1.5xULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • QTc corrected by Fridericia's (QTcF) formula>450 milliseconds (msec)
  • Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or 12-lead electrocardiogram.
  • 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) before the first dose of study medication and until study completion, unless in the opinion of the investigator and GlaxoSmithKline Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units for females and >21 units for males. One unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Urinary nicotine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. Limit of >500 nanogram/mL.
  • Involved in any activities likely to result in any significant decrease or increase in body weight during the study period (e.g. 'crash' dieting, bodybuilding).
  • 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 Medical Monitor, contraindicates their participation.
  • Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
  • A positive test for human immunodeficiency virus antibody.
  • Subjects with known, pre-existing helminthes infestation within 6 months prior to Day 1.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • A positive pre-study drug/alcohol screen.
  • A vulnerable subject. Defined as individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
  • Subjects who work for the Sponsor, contract research organization, or one of the study centers.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03014674
Other Study ID Numbers  ICMJE 204958
2016-002405-19 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com/Posting.aspx?ID=20060
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date November 2019

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