Aura Adolescent PK Study GSK2829332

NCT01653483 | Withdrawn Phase 2

• 1 other identifier: 116213
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, double-blind, placebo-controlled, repeat dose, 2-period, incomplete block, crossover, safety and pharmacokinetic (PK) study to evaluate 3 once-daily doses of umeclidinium (GSK573719; UMEC) in adolescent asthma subjects aged 12 through 17 years,) who are currently using asthma medications that do not contain inhaled corticosteroids (non-ICS). The objectives are to investigate safety and tolerability, and PK after a 7-day (+2) repeat once-daily dose of UMEC (15.6, 62.5, and 250 mcg) in asthmatic adolescent subjects. Safety endpoints will include reported adverse events, vital signs, ECGs, clinical laboratory tests, and rescue albuterol use. The PK endpoints will include serial PK (plasma and urine) concentrations and derived parameters. Twenty four subjects will be randomized to participate in the study for up to 7 weeks (including: an initial screening visit, a 7 to 14-day run-in, and 2 treatment periods each of 7 (+2) day duration, with a washout period of 7-14 days between treatment periods). There will be a Follow-up Visit approximately one week after the end of the second treatment period. Subjects will refrain from using rescue medication for 4 hours prior to any clinic visits, unless for emergency. During each treatment period, study medication will be taken once in the morning until the morning of Day 7 (+2 days) when subjects will return to the clinic for study assessments and take the last dose of study medication. On Day 7 (+2), subjects will remain in the clinic overnight for serial assessments (ECG, and PK plasma and urine samples over the 24-hours).

Conditions

Asthma

Keywords

Asthma; Umeclidinium; Adolescent; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Subject safety as measured by serial ECGs and vital signs measured on Days 7 of each treatment period and the number (and frequency) of subjects who experience adverse events after repeat doses of GSK573719

  Assessment of safety and tolerability, including: reported adverse events, clinical laboratory measurements, vital signs (heart rate and blood pressure), and electrocardiographic (ECG) parameters.

  Through the expected 7 day duration for each of 2 treatment periods.

Secondary Outcomes (2)

• Subject safety as measured by ECGs and vital signs measures on Day 1 of each treatment period

  Through the expected 6 hour duration of in clinic stay

• Pharmacokinetic parameters such as Cmax, AUC, half-life, Tmax of GSK573719 after repeat dosing.

  predose, 5, 15 and 30 minutes and, 1, 2, 4, 6, 8, 12, and 24, hours on Day 7 of dosing

Study Arms (2)

GSK573719

EXPERIMENTAL

Investigational treatment - Swedish Orange Coloured, opaque hard gelatin capsule

Drug: GSK573719matched-placebo

GSK573719 matched-placebo

PLACEBO COMPARATOR

Placebo

Drug: GSK573719

Interventions

GSK573719 DRUG

Novel Dry-Powder Inhaler

Also known as: umeclidinium

GSK573719 matched-placebo

GSK573719matched-placebo DRUG

Novel Dry-Powder Inhaler

GSK573719

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Informed consent: At least one parent/guardian has signed and dated the written informed consent prior to admission to the study. This will be accompanied by informed assent from the subject for children aged 12 through 17 years.
• Type of Subject: Outpatients. However subjects will remain in the clinic overnight at the end of each treatment period for serial safety and PK blood and urine assessments over a 24-hour period.
• Age: subjects aged 12 through 17 years (inclusive) at Visit 1 (a subject may not participate if the subject's 18th birthday would occur during the conduct of the study). Note: The study population will include an adequate representation of subjects throughout the ages of 12 to 17 years with at least 4 subjects 12 or 13 years of age and no more than 4 subjects 16 or 17 years of age.
• Weight: Subjects must weigh at least 32kg.
• Male or Eligible Female. Eligible being defined as of non-childbearing potential or childbearing potential using an acceptable method of birth control consistently and correctly. Note: To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined below: Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial and for a period after the trial to account for elimination of the drug (minimum of 6 days); Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; Implants of levonorgestrel or etonogestrel; Injectable progestogen; Oral contraceptive (either combined or progestogen alone); Estrogenic vaginal ring; Percutaneous contraceptive patches; Any intrauterine device (IUD) with a documented failure rate of less than 1% per year; Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); Male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository); Contraceptive transdermal patch, Ortho Evra (if the subject is less than 198 pounds \[90kg\]); Female subjects should not be enrolled if they are pregnant or lactating or if they plan to become pregnant during the time of study participation. A serum pregnancy test is required of all females and will be performed at the initial screening visit (Visit 1). In addition, a urine pregnancy test will be performed as in the Table of Time and Events.
• Understand protocol requirements: The subject and parent/guardian are able to understand and comply with protocol requirements, instructions, and protocol stated restrictions. The parent or guardian must have the ability to read, write, and record diary information collected throughout the study. The parent or guardian must have the ability to manage study drug administration.
• Diagnosis: diagnosis of asthma as defined by the National Institutes of Health \[NIH, 2007\] at least 6 months prior to Visit 1.
• Severity of Disease: A best pre-bronchodilator AM FEV1 of greater than and equal to 80% of the predicted normal value at the Visit 1 (screening) visit. Percent predicted normal values will be based upon: NHANES III (Hankinson, 1999) for the primary race/ethnicity of the subject (e.g Mexican-American, African-American/African heritage, Caucasian); Multiethnic spirometric assessments (Hankinson, 2010) for the primary race/ethnicity of the subject (e.g Asian).
• Current Anti-Asthma Therapy: Subjects must demonstrate a need for use of a non-corticosteroid medication as shown by having or received a prescription for either of the following for greater than and equal to 12 weeks preceding Visit 1 (and with no ICS used for at least 12 weeks prior to screening): a non-corticosteroid controller (e.g., theophylline, cromolyn, nedocromil, leukotriene modifiers \[e.g. montelukast, zafirlukast\], etc.), with or without SABA; a SABA bronchodilator such as albuterol.
• Short-Acting Beta2-Agonists (SABAs): All subjects must be able to replace their current SABA treatment with albuterol aerosol inhaler at Visit 1, as needed, for the duration of the study. Subjects must be judged capable of withholding albuterol for at least 4 hours prior to study visits.

You may not qualify if:

• Tobacco Use: A subject may not have used inhaled tobacco products (i.e., cigarettes, cigars, or pipe tobacco) or have historical use of tobacco products. Includes, urinary cotinine or CO breath test levels at screening that is indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Previous Use of Study Drug or Investigational Products: Previous use of UMEC excludes a subject or 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).
• Compliance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, disease, or geographical location which seems likely (in the opinion of the investigator) to impair compliance with any aspect of this study protocol, including visit schedule and completion of the daily diaries.
• Alcohol or substance abuse: Subjects with any history of alcohol use or substance abuse prior to screening, or use of, at any time during the study.
• Viral Hepatitis: A positive Hepatitis B surface antigen or positive Hepatitis C antibody pre-study or at Visit 1.
• Wards of State: Children who are wards of the state or government.
• Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
• Pregnancy: Pregnant females as determined by positive serum hCG test at screening or prior to dosing.
• Lactation: Lactating females.
• History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea requiring non-invasive ventilator support, respiratory arrest, hypoxic seizures or asthma-related syncopal episode(s).
• Asthma Exacerbation: A subject must not have a history of a severe asthma exacerbation within 12 weeks prior to Visit 1. A severe asthma exacerbation is defined as deterioration of asthma requiring the use of systemic corticosteroids (oral, or injection) for at least 3 days or an inpatient hospitalization or emergency department visit due to asthma that required systemic corticosteroids.
• Signs or symptoms of unstable asthma: Defined as: During the 7 days immediately preceding a visit, at least 3 days in which greater than and equal to 12 inhalations/day of albuterol/salbutamol were used; or A symptom score of greater than and equal to 4 on at least 3 consecutive days during the previous 7 days (defined as the subject experiencing symptoms for most of the day which affected normal daily activities); or at the discretion of the Investigator
• Respiratory Infection expected to affect the subject's ability to participate in the study: Within 4 weeks prior to Visit 1 a subject has had a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved and has led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
• Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.
• Diseases Preventing Use of Anticholinergics: Diagnosis of narrow-angle glaucoma, or bladder neck obstruction that in the opinion of the study investigator or GSK medical monitor would pose a safety risk with use of an inhaled anticholinergic.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Asthma

Interventions

GSK573719

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: July 31, 2012
• Study Start: September 1, 2012
• Primary Completion: September 1, 2012
• Study Completion: March 1, 2013
• Last Updated: November 12, 2012

Record last verified: 2012-11