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Dolutegravir Pediatric Liquid Formulation Study

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: NCT03921723
Recruitment Status : Active, not recruiting
First Posted : April 19, 2019
Last Update Posted : June 21, 2019
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Tracking Information
First Submitted Date  ICMJE April 17, 2019
First Posted Date  ICMJE April 19, 2019
Last Update Posted Date June 21, 2019
Actual Study Start Date  ICMJE May 7, 2019
Estimated Primary Completion Date July 8, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
  • Area under the plasma concentration time curve from time zero to the last quantifiable time point (AUC[0-t]) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • AUC from time zero to infinity (0-inf) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • Maximum observed concentration (Cmax) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03921723 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2019)
  • Absorption lag time (tlag) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • Time of maximum observed concentration (tmax) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • Time of last quantifiable concentration (t) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • Elimination half-life (t½) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • Apparent elimination rate constant (lambda z) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • Percentage of AUC(0-inf) extrapolated (%AUCex) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • AUC from time zero to 24 hours (AUC[0-24]) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • AUC from time zero to 72 hours (AUC[0-72]) following administration of DTG [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of DTG
  • Apparent oral clearance (CL/F) following administration of Dolutegravir [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of Dolutegravir
  • Apparent oral volume of distribution (Vz/F) following administration of Dolutegravir [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of Dolutegravir
  • Last quantifiable concentration (Ct) following administration of Dolutegravir [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of Dolutegravir
  • Concentration at 24h post-dose (C24) following administration of Dolutegravir [ Time Frame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 48 and 72 hours post-dose ]
    Blood samples will be collected for pharmacokinetic analysis of Dolutegravir
  • Change from Baseline in blood pressure [ Time Frame: Baseline and Up to Week 10 ]
    Systolic and diastolic blood pressure of subjects will be measured in a supine position after at least 5 minutes of rest with a completely automated device.
  • Change from Baseline in heart rate [ Time Frame: Baseline and Up to Week 10 ]
    Heart rate of subjects will be measured in a supine position after at least 5 minutes of rest.
  • Number of subjects with adverse events and serious adverse events [ Time Frame: Up to Week 10 ]
    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward medical occurrence resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as serious adverse event.
  • Number of subjects with toxicity grading for hematology parameters [ Time Frame: Up to Week 10 ]
    Blood samples will be collected from subjects for the analysis of hematology parameters as a measure of safety, including platelet count, red blood cell, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, percent reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils.
  • Number of subjects with toxicity grading for clinical chemistry parameters [ Time Frame: Up to Week 10 ]
    Blood samples will be collected from subjects for the analysis of clinical chemistry parameters as a measure of safety, including blood urea nitrogen, potassium, aspartate aminotransferase, total bilirubin, indirect bilirubin, direct bilirubin, albumin, creatinine, sodium, alanine aminotransferase, total protein, glucose (fasted), calcium, alkaline phosphatase, and creatine kinase.
  • Number of subjects with toxicity grading for urine parameters [ Time Frame: Up to Week 10 ]
    Urine samples will be collected from subjects for the analysis of urinalysis parameters as a measure of safety, including specific gravity and potential of hydrogen (pH) of urine, presence of glucose, protein, blood, and ketones in urine by dipstick test. Microscopic examination will be performed if blood or protein is abnormal.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dolutegravir Pediatric Liquid Formulation Study
Official Title  ICMJE Non-randomized, Sequential, Fixed-sequence Evaluation of Prototype Dolutegravir Liquid Formulations Versus 5mg Dolutegravir Dispersible Tablets Following Single-dose Fasted-state Administrations to Normal Healthy Adult Participants
Brief Summary This is an open-label, single-center, single dose, non-randomized, sequential, fixed-sequence study, which will evaluate pharmacokinetics (PK) of dolutegravir (DTG) in healthy adult subjects. The study will contain 6 periods with five prototype liquid formulations for evaluation in fasted state. In period 1, 2 and 3 single reference dose of 2 dispersible tablets of 5 milligram DTG will be administered and at least 2 liquid prototype DTG formulations (containing a target total dose of 10mg DTG). There will be a wash-out period of 7 days between each period. In period 4 through 6, there would be options to evaluate additional prototype liquid formulations. The total duration of study will be up to 17 weeks. DTG has been found to be safe and effective in adults infected with human immunodeficiency virus (HIV), and DTG liquid formulation are being developed for the treatment of HIV-infected pediatric subjects who weigh less than 25 kilograms (Kgs). Approximately 18 subjects will be enrolled in this study.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
The study is non-randomized 6 period, 6 way fixed sequential design.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: Dolutegravir dispersible tablet
    DTG will be available as an oral tablet with dosing strength of 5 mg 2 tablet will be dispersed in water will be administered orally for prescribed regimen.
  • Drug: Dolutegravir oral suspension
    DTG will be available as an oral suspension with dosing strength of 5 mg per milliliter (ml) or 2 mg per ml with miglyol 812N or ethyl cellulose in miglyol 812N as vehicle for suspension administered orally for prescribed regimen.
  • Drug: Dolutegravir oral solution
    DTG will be available as an oral solution with dosing strength of 2 mg per ml will be administered orally for prescribed regimen.
Study Arms  ICMJE Experimental: Subject receiving Dolutegravir 10 mg
Subject will receive a prototype equivalent to DTG 10 mg liquid formulation in period 1, a prototype equivalent to DTG 10 mg liquid formulation in period 2, a DTG 10 mg dispersible tablet in Period 3, each period will be separated by washout period of >= 7 days, if required a prototype equivalent to DTG 10 mg liquid formulation in period 4, a prototype equivalent to DTG 10 mg liquid formulation in period 5, and a prototype equivalent to DTG 10 mg liquid formulation in period 6 will be evaluated.
Interventions:
  • Drug: Dolutegravir dispersible tablet
  • Drug: Dolutegravir oral suspension
  • Drug: Dolutegravir oral solution
Publications * Not Provided

*   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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 17, 2019)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 8, 2019
Estimated Primary Completion Date July 8, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
  • Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac evaluation.
  • Body weight >= 50 kg (110 pounds [lbs]) for men and >=45 kg (99 lbs) for women and body mass index (BMI) within the range 18.5-31.0 kilogram per meter square (kg/m^2) (inclusive).
  • Male and female subjects will be part of study. A female subject is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP).
  • Additional requirements for pregnancy testing, if needed, during and after study intervention; The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Subject should be capable of giving signed informed consent as which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).

Exclusion Criteria:

  • History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
  • Abnormal blood pressure as determined by the investigator.
  • Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
  • Bilirubin >1.5times ULN (isolated bilirubin >1.5 times 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).
  • QT correction using Fridericia Formula (QTcF) >450 millisecond (msec)
  • Past or intended use of over-the-counter or prescription medication (including herbal medications) within 7 days prior to dosing. Paracetamol.
  • History of allergy or sensitivity to DTG.
  • Participation in the study would result in loss of blood or blood products in excess of 500 mL within 56 days.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Current enrollment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research.
  • Presence of Hepatitis B surface antigen (HBsAg), or a positive hepatitis B core antibody with a negative hepatitis B surface antibody at screening.
  • Positive Hepatitis C antibody test result at screening: Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.
  • Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.
  • Positive pre-study drug/alcohol screen.
  • Positive HIV antibody test.
  • Regular use of known drugs of abuse.
  • Regular alcohol consumption within one month prior to the study defined as: For the United Kingdom an average weekly intake of >14 units for males or females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 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 NCT03921723
Other Study ID Numbers  ICMJE 209354
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
Product Manufactured in and Exported from the U.S.: Yes
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 will be made available within 6 months of publishing the results of the primary endpoints of the study.
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: http://clinicalstudydatarequest.com
Responsible Party ViiV Healthcare
Study Sponsor  ICMJE ViiV Healthcare
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials ViiV Healthcare
PRS Account ViiV Healthcare
Verification Date June 2019

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