Primary objective:* To compare the bioavailability of different dry powder formulations of tiotropium bromide in healthy volunteersSecondary objectives:* To compare the safety and tolerability of different dry powder formulations of tiotropium…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* The area under the plasma concentration-time curve from time zero to time t
of the last measured concentration above the limit of quantification (AUC0-t).
* The area under the plasma concentration-time curve from zero to infinity
(AUC0-*).
* The maximum plasma concentration (Cmax).
* The time to reach maximum plasma concentration (tmax).
* The terminal elimination rate constant (*z) with the respective half-life
(t*).
Secondary outcome
* (Treatment emergent) adverse events
* Physical examination
* Vital signs
* ECG
* Spirometry
* Clinical safety laboratory
Background summary
Phargentis is developing a tiotropium bromide DPI product to aim for a generic
by taking into consideration intellectual property issues for all aspects
related to the drug substance, formulation, capsule selection, and inhaler
device. Phargentis has developed two DPI formulations, which are expected to be
comparable to the reference product Spiriva HandiHaler marketed by Boehringer
Ingelheim. The two formulations differ with respect to the original product for
the polymorphic form of the API and for the composition of the capsule shells
(Hydroxypropylmethylcellulose capsule shells instead of PEG/gelatin capsule
shells used by the originator). The formulations are supposed to be inhaled by
means of an inhaler that is comparable to the Reference Device HandiHaler.
Taking into account the features of the active ingredient and the used
excipients, the sponsor concluded that there was no need to perform additional
pre-clinical safety studies with their new tiotropium bromide inhalation
powders.
The aim of the present study is to obtain preliminary pharmacokinetic data on
the two Phargentis test formulations and the reference product which will allow
for the selection of the final Phargentis formulation and the design and sample
size calculation of the pivotal bioequivalence study.
Study objective
Primary objective:
* To compare the bioavailability of different dry powder formulations of
tiotropium bromide in healthy volunteers
Secondary objectives:
* To compare the safety and tolerability of different dry powder formulations
of tiotropium bromide in healthy volunteers
Study design
This is an open label, randomized, single inhaled dose, three -way cross over
pilot study with a wash-out of at least two weeks between successive dosing
occasions.
Intervention
After assessing eligibility during a screening period of up to 4 weeks, 18
subjects will be enrolled in this study. The study will consist of 3 periods,
each separated by a wash-out period of at least 2 weeks between successive
dosing occasions. During each period, subjects will come to the study center on
the day before administration (Day -1) of the study drug, for baseline
assessments, inhalation instructions/training on the correct use of the
inhalers and to re*confirm eligibility. On Day 1, all subjects will receive one
single dose of tiotropium (consisting of two capsules) under fasted conditions.
Blood samples for determination of tiotropium will be collected pre*dose and at
specified time points up to Day 7 post*dose. Safety evaluations including
adverse events recording and spirometry will be obtained at regular time points
throughout the study. Subjects will be discharged from the clinic in the
morning of Day 2. Subjects will return to the clinic for at least 4 more
ambulant visits up to Day 7. After the blood sample on Day 7 of the last study
period, subjects will undergo an End*of*study examination.
The overall study duration per subject will be approximately 10 weeks.
Study burden and risks
This study is being conducted in healthy volunteers. There are no anticipated
benefits of the IMPs. Please see the IMP information (IB and SmPC) for further
information.
Via Figino 6
Barbengo/Lugano 6917
CH
Via Figino 6
Barbengo/Lugano 6917
CH
Listed location countries
Age
Inclusion criteria
1. Subjects must be healthy male or female subjects 18-50 years of age, inclusive.
2. Subjects must have normal lung function at Screening and prior to first dosing according to the investigator, e.g. FEV1 * 80% of the predicted normal value (inclusive).
3. Subject must be able to adequately follow the inhalation instructions and inhale correctly through both devices.
Exclusion criteria
1. A history of a clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) or any other clinically significant abnormality or disease.
2. An upper and/or lower respiratory tract infection within 3 weeks of Screening.
3. Any chronic and/or symptomatic upper or lower airway disease such as asthma, COPD, bronchiectasis, sarcoidosis, lung cancer, allergic airway disease (e.g. pollen allergy inside the relevant season or symptomatic to pets while daily exposed to them).
4. Current smokers (smoked in the previous 12 months or stopped smoking less than 12 months prior to Screening) or ex-smokers with more than 10 pack-year smoking history (e.g., at least 1 pack/day for 10 years, or 2 packs/day for 5 year).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002705-35-NL |
| CCMO | NL62461.056.17 |