Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, pulmonary, inhalation
Brief summary
The purpose of this study was to evaluate the efficacy, safety, and tolerability of single doses of trospium inhalation powder (TrIP) administered to subjects with chronic obstructive pulmonary disease (COPD).
Detailed description
This was a single-center, randomized, double-blind, cross-over, placebo-controlled study. Following screening, each eligible subject was randomized to a dosing sequence. Study subjects received a total of 5 single doses, each separated by a 3- to 14-day washout period. Doses A, B, C, and D were administered in a double-blind fashion, in sequences generated by a 4-period Latin square design. The 4 dosing sequences were: ABCD, BDAC, CADB, and DCBA. Dose E was administered in an open-label fashion as the final dose in each dosing sequence for all subjects. Subjects reported to the clinic the evening prior to each dose. Protocol assessments were carried out until 24 hours postdose. Pulmonary function testing (via spirometry) was captured at specified timepoints at baseline as well as before and after dosing. Other efficacy and safety outcomes were assessed according to protocol. Blood sampling was performed for assessment of trospium concentrations at specified timepoints.
Interventions
DRUGPlacebo
Supplied as an empty size-2 capsule and administered as a single dose via C2S inhaler.
DRUGTrIP-2D
Trospium inhalation powder containing 100 mcg TrCl (trospium chloride), supplied as dry powder in size-2 capsules and administered as a single dose via C2S inhaler.
DRUGTrIP-2SS
Trospium inhalation powder containing 100 mcg TrCl (trospium chloride), supplied as dry powder in size-2 capsules and administered as a single dose via C2S inhaler.
DRUGTrIP-2SS + Foradil
Trospium inhalation powder containing 100 mcg TrCl (trospium chloride), plus foradil (12 mcg formoterol fumarate) supplied as dry powder in size-2 capsules and administered as a single dose via C2S inhaler.
Sponsors
Alkermes, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female COPD subjects between the ages of 40 and 80 years * Body mass index between 18 and 35 * Medically healthy (other than COPD) * FEV1/FVC less than or equal to 0.70 * Current non-smoker or able to abstain from smoking for at least 8 hours postdose * Within the previous 6 months, demonstrated improvement in FEV1 (greater than or equal to 10%) 1 hour following administration of ipratropium bromide inhalation (4 puffs) * Females of childbearing potential must agree to use an acceptable method of contraception for the duration of the study
Exclusion criteria
* Asthma in the last 10 years * Allergic rhinitis, atopy, cystic fibrosis, bronchiectasis, or tuberculosis * Bladder neck obstruction, including urinary retention or known symptomatic prostatic hypertrophy not controlled with medication * Narrow angle glaucoma * Tachyarrhythmia * Alcohol dependence or illicit drug abuse within the past year * Using long-term oxygen therapy * Female subjects who are pregnant or breastfeeding * Participating in another clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L) | 15 minutes to 24 hours post-treatment | Following screening, each subject was randomized to a sequence of 5 dosing periods (Doses A, B, C, D, and E). Each period was separated by a 3- to 14-day washout interval. The dosing formulations were as follows: Dose A = placebo Dose B = TrIP-2D (100 μg TrCl formulated in leucine and DPPC) Dose C = TrIP-2SS (100 μg TrCl formulated in leucine and sodium saccharin) Dose D = TrIP-2D (400 μg TrCl) Dose E = TrIP-2SS (100 μg TrCl) + Foradil (12 μg formoterol fumarate) FEV1 (L)was measured at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 Response to Treatment | Up to 24 hours post-treatment | Response was defined as the number of subjects reporting a post-treatment FEV1 of ≥12% (or 200 mL) above baseline. |
| Time to Maximum Plasma Concentration (Tmax) of Trospium After Single Administrations of TrIP | up to 24 hours post-treatment | Tmax is reported as median (range) of hours to reach maximum trospium concentration in plasma. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Following screening, each subject was randomized to a sequence of 5 dosing periods (Doses A, B, C, D, and E). Each period was separated by a 3- to 14-day washout interval. Doses A, B, C, and D were administered in a double-blind fashion. Dose E was administered in an open-label fashion.
The dosing formulations were as follows:
Dose A = placebo Dose B = TrIP-2D (100 μg TrCl formulated in leucine and DPPC) Dose C = TrIP-2SS (100 μg TrCl formulated in leucine and sodium saccharin) Dose D = TrIP-2D (400 μg TrCl) Dose E = TrIP-2SS (100 μg TrCl) + Foradil (12 μg formoterol fumarate) | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age Continuous | 63.0 years STANDARD_DEVIATION 8.9 |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 24 | 1 / 24 | 2 / 24 | 4 / 24 | 1 / 24 | 1 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L)
Following screening, each subject was randomized to a sequence of 5 dosing periods (Doses A, B, C, D, and E). Each period was separated by a 3- to 14-day washout interval. The dosing formulations were as follows: Dose A = placebo Dose B = TrIP-2D (100 μg TrCl formulated in leucine and DPPC) Dose C = TrIP-2SS (100 μg TrCl formulated in leucine and sodium saccharin) Dose D = TrIP-2D (400 μg TrCl) Dose E = TrIP-2SS (100 μg TrCl) + Foradil (12 μg formoterol fumarate) FEV1 (L)was measured at 15 and 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours postdose.
Time frame: 15 minutes to 24 hours post-treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TrIP-2SS (100mcg) | Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L) | 1.707 Liters | Standard Deviation 0.528 |
| TrIP-2SS (100mcg) + Foradil (12mcg) | Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L) | 1.696 Liters | Standard Deviation 0.521 |
| TrIP-2D (100mcg) | Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L) | 1.672 Liters | Standard Deviation 0.528 |
| TrIP-2D (400mcg) | Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L) | 1.676 Liters | Standard Deviation 0.516 |
| Placebo | Spirometry Parameter: Peak Forced Expiratory Volume in 1 Second(FEV1)in Liters (L) | 1.508 Liters | Standard Deviation 0.545 |
Comparison: The difference between the active treatment was compared to placebo. For a null hypothesis, the difference would equal 0 (zero).p-value: <0.0001ANCOVA
Secondary
FEV1 Response to Treatment
Response was defined as the number of subjects reporting a post-treatment FEV1 of ≥12% (or 200 mL) above baseline.
Time frame: Up to 24 hours post-treatment
Population: All 24 randomized subjects were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TrIP-2SS (100mcg) | FEV1 Response to Treatment | 23 Participants |
| TrIP-2SS (100mcg) + Foradil (12mcg) | FEV1 Response to Treatment | 22 Participants |
| TrIP-2D (100mcg) | FEV1 Response to Treatment | 22 Participants |
| TrIP-2D (400mcg) | FEV1 Response to Treatment | 21 Participants |
| Placebo | FEV1 Response to Treatment | 14 Participants |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Trospium After Single Administrations of TrIP
Tmax is reported as median (range) of hours to reach maximum trospium concentration in plasma.
Time frame: up to 24 hours post-treatment
Population: The PK population consisted of all subjects who received active study medication and had sufficient concentration data to facilitate calculation of the PK parameters or descriptive statistics of concentrations of trospium.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TrIP-2SS (100mcg) | Time to Maximum Plasma Concentration (Tmax) of Trospium After Single Administrations of TrIP | 0.08 Hours |
| TrIP-2SS (100mcg) + Foradil (12mcg) | Time to Maximum Plasma Concentration (Tmax) of Trospium After Single Administrations of TrIP | 0.08 Hours |
| TrIP-2D (100mcg) | Time to Maximum Plasma Concentration (Tmax) of Trospium After Single Administrations of TrIP | 0.08 Hours |
| TrIP-2D (400mcg) | Time to Maximum Plasma Concentration (Tmax) of Trospium After Single Administrations of TrIP | 0.08 Hours |