ROTAHALER Device Optimization Study

NCT01890863 | Completed Phase 1

• 1 other identifier: 200260
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare the pharmacokinetic (PK) of Fluticasone Propionate/Salmeterol combination (FSC) 100/50 micrograms (mcg) delivered via the capsule-based inhaler (Rdpi) relative to FSC 100/50 mcg delivered via the multi-dose dry powder inhaler (Ddpi) to establish whether the Rdpi inhaler has exposure (in terms of fluticasone propionate area under time concentration curve \[AUC\] and Salmeterol maximum concentration \[Cmax\]) no greater than 1.2500 compared to the Ddpi, sufficient to allow progression to Phase 3. This study will enroll 36 healthy adult male and female subjects and each subject will be allocated to one of two sequences and will participate in four treatment periods, receiving each of the treatments twice.

Conditions

Asthma

Keywords

asthma; fluticasone propionate/salmeterol; PK equivalence; COPD; pharmacokinetics; fluticasone propionate/salmeterol in a capsule-based inhaler; fluticasone propionate/salmeterol in a multi-dose dry powder inhaler; Respiratory

Outcome Measures

Primary Outcomes (1)

• Composite of PK parameters of FSC delivered via the Rdpi relative to FSC delivered via the Ddpi

  PK Parameters include: area under the plasma fluticasone propionate concentration-time curve over dosing interval (AUCtau), salmeterol maximum plasma concentration-time curve on the last day of each study treatment period (Cmax).

  PK samples will be collected at pre-dose, 5 minutes (mins), 10 mins, 30 mins, 1, 2, 4, 8, 10, and 12 hours post dose on Day 4 of each treatment period.

Secondary Outcomes (4)

• Composite of PK parameters of FSC delivered via the Rdpi relative to FSC delivered via the Ddpi

  PK samples will be collected at pre-dose, 5 minutes (mins), 10 mins, 30 mins, 1, 2, 4, 8, 10, and 12 hours post dose on Day 4 of each treatment period.

• Number of participants with adverse events (AEs) as measure of safety and tolerability.

  35 days.

• Laboratory parameters as a measure of safety and tolerability.

  35 days

• Vital sign measurement as measure of safety and tolerability.

  35 days.

Study Arms (2)

Sequence 1

EXPERIMENTAL

Subjects will receive treatment A and B in following sequence in four treatment periods (one treatment per period): ABBA, where treatment A is 7 doses of FSC (100/50 mcg) delivered via the Ddpi and treatment B is 7 doses of FSC (100/50mcg) delivered via the Rdpi. Subjects will be dosed twice daily for 3 days and once on the fourth day in the morning (a single inhalation of 100/50mcg per dose).

Drug: Fluticasone Propionate / Salmeterol Xinafoate DISKUS; Drug: Fluticasone Propionate / Salmeterol Xinafoate ROTACAP

Sequence 2

EXPERIMENTAL

Subjects will receive treatment A and B in following sequence in four treatment periods (one treatment per period): BAAB, where treatment A is 7 doses of FSC (100/50 mcg) delivered via the Ddpi and treatment B is 7 doses of FSC (100/50mcg) delivered via the Rdpi. Subjects will be dosed twice daily for 3 days and once on the fourth day in the morning (a single inhalation of 100/50mcg per dose).

Drug: Fluticasone Propionate / Salmeterol Xinafoate DISKUS; Drug: Fluticasone Propionate / Salmeterol Xinafoate ROTACAP

Interventions

Fluticasone Propionate / Salmeterol Xinafoate DISKUS DRUG

Fluticasone propionate and salmeterol xinafoate combination as a dry powder inhaler for oral inhalation with unit dose strength of 100/50 mcg (available in blister pack) administered via DISKUS (Ddpi) device.

Sequence 1; Sequence 2

Fluticasone Propionate / Salmeterol Xinafoate ROTACAP DRUG

Fluticasone propionate and salmeterol xinafoate combination as a dry powder inhaler for oral inhalation with unit dose strength of 100/50 mcg (available in blister pack) administered via ROTAHALER (Rdpi) device.

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• Body mass index within the range 18 to 35 kilograms/meter squared (m\^2) (inclusive).
• A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy (for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records); or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \> 40 milli international unit/mililiter \[mL\] and estradiol \< 40 picogram/mL \[\<147 picomoles/liter\] is confirmatory. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• Child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotropin (hCG) test at screening or prior to dosing.
• Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 2 days post-last dose.
• OR has only same-sex partners, when this is her preferred and usual lifestyle.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Alanine aminotransferase, alkaline phosphatase and bilirubin \<= 1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 %).
• Based on single or averaged QT interval corrected (QTc) values of triplicate electrocardiograms (ECGs) obtained over a brief recording period: QT duration corrected for heart rate by Fridericia's formula (QTcF)\<450 millisecond (msec), and QT duration corrected for heart rate by Bazett's formula (QTcB)\<480 msec in subjects with Bundle Branch Block.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of \>21 units for males or \>14 units for females. In Australia one unit (= standard drink) is equivalent to 10 grams of alcohol: 270 mL of full strength beer (4.8%), 375mL of mid strength beer (3.5%), 470 mL of light beer (2.7%), 250 mL pre-mix full strength spirit (5%), 100 mL of wine (13.5%) and 30 mL of spirit (40%)
• 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 GSK Medical Monitor, contraindicates their participation.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• A positive pre-study drug/alcohol screen.
• A positive test for human immuno virus antibody.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Links

• Results for study 200260 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive

Interventions

Fluticasone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2013
• First Posted: July 2, 2013
• Study Start: August 5, 2013
• Primary Completion: September 30, 2013
• Study Completion: September 30, 2013
• Last Updated: June 19, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)