Chronic Obstructive Pulmonary Disease (COPD), Asthma
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of single doses of LAS190792 administered by inhalation to patients with mild persistent asthma and moderate to severe chronic obstructive pulmonary disease (COPD) and also to assess the ability of LAS190792 to produce bronchodilation (opening of the airways).
Detailed description
This study is an integrated Phase I protocol divided into 2 parts. Part one: a single ascending dose study (6 LAS190792 dose levels) in 16 male subjects with mild asthma. LAS190792 will be administered (by the Genuair® inhaler) under supervision at the study centre, according to the randomisation scheme. One dose level will be administered per week with 2 to 3 weeks between each dose level for the safety and pharmacokinetic data review. Part two: A 5-way , crossover, single dose study (of LAS190792 \[two doses\], indacaterol, tiotropium and placebo) in 40 male and non-childbearing potential women subjects with moderate to severe COPD. Each treatment period will be separated by a washout period of at least 7 to 14 days. The aim is to ensure at least 30 subjects complete Part 2 of the study. The primary comparison for bronchodilation will be between LAS190792 doses and placebo. Other treatment comparisons (indacaterol or tiotropium vs placebo and LAS190792 vs indacaterol or tiotropium) will be considered additional.
Interventions
DRUGLAS190792 Dose 1
DRUGLAS190792 Dose 2
DRUGLAS190792 Dose 3
DRUGLAS190792 Dose 4
DRUGLAS190792 Dose 5
DRUGLAS190792 Dose 6
DRUGLAS190792 Dose 1 (Part 2)
DRUGLAS190792 Dose 2 (Part 2)
DRUGTiotropium 18 μg
DRUGPlacebo
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
(PART 1): * Adult male subjects aged 18 to 70 years * Body mass index (BMI) 18.5 to 30 kg/m2 at screening * Clinical diagnosis of mild persistent asthma (according to GINA guidelines) for at least 6 months prior to screening * Ability to change current asthma therapy, to discontinue previous prescribed medications after signature of informed consent as per required washout periods * Screening FEV1 value of ≥70% of the predicted normal value after a washout of at least 5 h for short-acting beta2-agonists and 72 h for long-acting beta2-agonists * FEV1 reversibility of ≥12% and an absolute increase of at least 200 mL over the baseline value within 30 min after inhalation of 400 µg of salbutamol * Subjects using intermittent salbutamol and / or subjects on a stable dose or regimen of low dose ICS (as defined by the GINA guidelines) at least 4 weeks prior to screening * Predose FEV1 value of first treatment period within the range of ±20% of the FEV1 measured at screening prior to salbutamol inhalation * Subjects who are otherwise healthy as determined by medical history, physical examination, 12-lead ECG findings * Normal blood pressure (defined as SBP between 100 and 140 mmHg, and DBP between 50 and 90 mmHg) at screening, measured after resting in supine position for 5 minutes. * Subjects whose clinical laboratory test results are not clinically relevant and are acceptable to the Investigator * Subjects who are negative for hepatitis B surface antigen (HBsAg), hepatitis B core (HBc) antibody (IgM), hepatitis C antibody and human immunodeficiency virus (HIV) I and II antibodies at screening * Subjects who are able and willing to provide written informed consent * Subjects able to perform repeatable pulmonary function testing for FEV1 according to the American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005 criteria at screening Inclusion Criteria (PART 2): * Adult male and non-childbearing potential women subjects aged ≥40 years with a clinical diagnosis of stable moderate to severe COPD according to GOLD guidelines at screening * Females must be of non-childbearing potential, confirmed at screening * Post-salbutamol FEV1 \<80% and ≥30% of the predicted normal value and post-salbutamol FEV1 / forced vital capacity (FVC) \<70% * Ability to change current COPD therapy, to discontinue previous prescribed medications after signature of informed consent * No evidence of clinically significant respiratory and / or cardiovascular conditions or laboratory abnormalities * No other relevant pulmonary disease or history of thoracic surgery * No contraindication to the use of anticholinergic drugs such as known symptomatic prostatic hypertrophy, bladder neck obstruction, narrow-angle glaucoma, or beta2-agonists usage * Subjects who are negative for HBsAg, HBc IgM, hepatitis C antibody and HIV I and II antibodies at screening * Subjects who are able and willing to provide written informed consent * Subjects able to perform repeatable pulmonary function testing for FEV1 according to the ATS / ERS 2005 criteria at screening
Exclusion criteria
(PART 1 and 2): * Subjects who do not conform to the above inclusion criteria * Current smokers, subjects with a smoking history during the last 12 months or subjects with a smoking history of more than 10 pack-years * Other relevant pulmonary disease or history of thoracic surgery * Subjects with a BMI ≥40 kg/m2 (only applicable for Part 2) * Subjects with any clinically relevant history or presence of abnormality from the medical history and/or physical examination (only applicable for Part 1) * Current evidence or recent history of any clinically significant and unstable disease (other than COPD) or abnormality that could put the subject at risk or could confound the results of the study (only applicable for Part 2) * Subjects with a surgical history clinically relevant for the purpose of the study * History of malignancy of any organ system, treated or untreated within the past 5 years, with the exception of localised basal cell carcinoma of the skin * Subjects with serious adverse reaction or serious hypersensitivity to Spiriva (for Part 2 only), indacaterol (for Part 2 only), or the formulation excipients (eg, lactose) or other drugs in the same pharmacologic class (for Part 1 and Part 2) * Current diagnosis of COPD (for Part 1 only) or history of / or current diagnosis for asthma (for Part 2 only) * Recent history of asthma / COPD exacerbation requiring hospitalisation or need for increased maintenance treatments for asthma / COPD within 6 weeks prior to screening or randomisation * Use of daily oxygen therapy \>10 h per day (for Part 2 only) * Use of systemic steroids for respiratory reasons within 3 months prior to screening * Lower respiratory tract infection within 6 weeks prior to screening or randomisation * Upper respiratory tract infection requiring antibiotics within 4 weeks prior to screening or randomisation * Current history of tuberculosis, bronchiectasis or other non-specific pulmonary disease * QTcF interval \>430 ms at screening or prior to randomisation, or history of long QT syndrome (for Part 1 only) * QTcF interval, \>450 ms for males and \>470 ms for females at screening or prior to randomisation, or history of long QT syndrome (for Part 2 only) * Subjects with a history of excessive use or abuse of alcohol or with a history of drug abuse within the past 2 years * Subjects who are positive for drugs of abuse and alcohol tests at screening and prior to randomisation * Donation or loss \>400 ml of blood and plasma within the previous 3 months prior to screening * Subjects consuming more than 14 (female subjects) or 21 (male subjects) units of alcohol a week * Subjects with a significant infection or known inflammatory process at screening or prior to randomisation * Subjects with acute gastrointestinal symptoms at the time of screening or prior to randomisation * Subjects with an acute infection such as influenza at the time of screening or prior to randomisation * Male subjects who do not agree to follow instructions to avoid pregnancies * Subjects who are not able to adhere to the restrictions on prior and concomitant medications * Subjects who intend to use any concomitant medication not permitted by the protocol or who have not undergone the required washout period for a particular prohibited medication * Subjects who have used any investigational drug within 3 months prior to screening or within the equivalent time of 6 half-lives of receiving the last administration, whichever is longer * Subjects who have received the last dose of investigational product more than 3 months ago but who are on an extended follow-up * Subjects who are vegans or who have medical dietary restrictions * Subjects unable to communicate reliably with the Investigator * Subjects who are unlikely to co-operate with the requirements of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects With ≥1 Treatment-emergent Adverse Event | 30 Days | Adverse events (AEs) are any unfavorable and unintended medical occurrence during the subject's participation in the study (including deterioration of a pre-existing medical condition, an abnormal value in a laboratory assessment, an ECG abnormality, a 12-lead 24-hour ECG-Holter abnormality, a blood pressure abnormal value, paradoxal bronchospasm or an abnormal finding in the physical examination) and will be coded using the current Medical Dictionary for Regulatory Activities (MedDRA). |
| Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | Day 2 | Trough is defined as the mean of the FEV1 values obtained at 23 hours and at 24 hours after morning investigational product administration. |
Secondary
| Measure | Time frame |
|---|---|
| Time to Maximum Observed Plasma Concentration (Tmax) | Up to 36 hours after investigational product administration |
| Maximum Observed Plasma Concentration (Cmax) | Up to 36 hours after investigational product administration |
| Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration | Up to 36 hours after investigational product administration |
Countries
United Kingdom
Participant flow
Recruitment details
This study was conducted at 2 centres in the UK. In part 1 of the study, the first patient was screened in September 2013 and the last patient visit was in February 2014. In part 2 of the study, the first patient was screened in March 2014 and the last patient visit was in October 2014.
Pre-assignment details
This was a 2-part study. Part 1: incomplete crossover, single ascending dose study of 2 cohorts randomised to fixed sequences of LAS190792 or placebo in 3 treatment periods. Part 2: 5-way complete crossover, single dose study of LAS190792 (100/400 μg), placebo, or active controls (indacaterol 150 μg, tiotropium 18 μg) in 5 treatment periods.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 - Cohort 1 LAS190792 5 μg, 50 μg, 200 μg All individuals in Part 1 - Cohort 1 who were randomised to treatment sequence LAS190792 5 μg, 50 μg, 200 μg in 3 treatment periods separated by washout periods of 28-42 days. | 2 |
| Part 1 - Cohort 1 Placebo, Then LAS190792 50 μg, 200 μg All individuals in Part 1 - Cohort 1 who were randomised to treatment sequence Placebo, then LAS190792 50 μg, 200 μg in 3 treatment periods separated by washout periods of 28-42 days. | 2 |
| Part 1 - Cohort 1 LAS190792 5 μg, Placebo, LAS190792 200 μg All individuals in Part 1 - Cohort 1 who were randomised to treatment sequence LAS190792 5 μg, Placebo, LAS190792 200 μg in 3 treatment periods separated by washout periods of 28-42 days. | 2 |
| Part 1 - Cohort 1 LAS190792 5 μg, 50 μg, Then Placebo All individuals in Part 1 - Cohort 1 who were randomised to treatment sequence LAS190792 5 μg, 50 μg, then Placebo in 3 treatment periods separated by washout periods of 28-42 days. | 2 |
| Part 1 - Cohort 2 LAS190792 20 μg, 100 μg, 400 μg All individuals in Part 1 - Cohort 2 who were randomised to treatment sequence LAS190792 20 μg, 100 μg, 400 μg in 3 treatment periods separated by washout periods of 28-42 days. | 2 |
| Part 1 - Cohort 2 Placebo, Then LAS190792 100 μg, 400 μg All individuals in Part 1 - Cohort 2 who were randomised to treatment sequence Placebo, then LAS190792 100 μg, 400 μg in 3 treatment periods separated by washout periods of 28-42 days. | 2 |
| Part 1 - Cohort 2 LAS190792 20 μg, Placebo, LAS190792 400 μg All individuals in Part 1 - Cohort 2 who were randomised to treatment sequence LAS190792 20 μg, Placebo, LAS190792 400 μg in 3 treatment periods separated by washout periods of 28-42 days. | 2 |
| Part 1 - Cohort 2 LAS190792 20 μg, 100 μg, Then Placebo All individuals in Part 1 - Cohort 2 who were randomised to treatment sequence LAS190792 20 μg, 100 μg, then Placebo in 3 treatment periods separated by washout periods of 28-42 days. | 3 |
| Overall Population - Part 2 All individuals involved in Part 2 (single-dose study of two doses of LAS190792 \[100 and 400 μg\], indacaterol, tiotropium or placebo, in 5 treatment periods separated by washout periods of 7-14 days). | 38 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Washout Between Periods 1 and 2 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Washout Between Periods 4 and 5 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Washout Between Periods 6 and 7 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Washout Between Periods 7 and 8 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Washout Between Periods 7 and 8 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1 - Cohort 1 LAS190792 5 μg, 50 μg, 200 μg | Part 1 - Cohort 1 Placebo, Then LAS190792 50 μg, 200 μg | Part 1 - Cohort 1 LAS190792 5 μg, Placebo, LAS190792 200 μg | Part 1 - Cohort 1 LAS190792 5 μg, 50 μg, Then Placebo | Part 1 - Cohort 2 LAS190792 20 μg, 100 μg, 400 μg | Part 1 - Cohort 2 Placebo, Then LAS190792 100 μg, 400 μg | Part 1 - Cohort 2 LAS190792 20 μg, Placebo, LAS190792 400 μg | Part 1 - Cohort 2 LAS190792 20 μg, 100 μg, Then Placebo | Total | Overall Population - Part 2 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Part 1 | 35 Years STANDARD_DEVIATION 8.5 | 34.5 Years STANDARD_DEVIATION 20.5 | 35 Years STANDARD_DEVIATION 4.2 | 37 Years STANDARD_DEVIATION 19.8 | 32.5 Years STANDARD_DEVIATION 6.4 | 41.5 Years STANDARD_DEVIATION 29 | 28 Years STANDARD_DEVIATION 1.4 | 34.3 Years STANDARD_DEVIATION 12.7 | 34.7 Years STANDARD_DEVIATION 12 | — |
| Age, Continuous Part 2 | — | — | — | — | — | — | — | — | 60.4 Years STANDARD_DEVIATION 5.9 | 60.4 Years STANDARD_DEVIATION 5.9 |
| Sex: Female, Male Part 1 Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Part 1 Male | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 17 Participants | 0 Participants |
| Sex: Female, Male Part 2 Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 18 Participants | 18 Participants |
| Sex: Female, Male Part 2 Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 20 Participants | 20 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 3 / 6 | 1 / 6 | 2 / 6 | 2 / 6 | 4 / 6 | 3 / 12 | 4 / 36 | 9 / 35 | 6 / 37 | 15 / 37 | 11 / 37 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 36 | 0 / 35 | 0 / 37 | 0 / 37 | 0 / 37 |
Outcome results
Primary
Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second)
Trough is defined as the mean of the FEV1 values obtained at 23 hours and at 24 hours after morning investigational product administration.
Time frame: Day 2
Population: Per Protocol Population: defined as all randomized subjects who satisfied the main inclusion / exclusion criteria, received investigational product, completed at least one treatment period, and did not present major violations to the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAS190792 5 µg (Part 1) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | -0.013 Liters | Standard Deviation 0.333 |
| LAS190792 20 µg (Part 1) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 0.161 Liters | Standard Deviation 0.131 |
| LAS190792 50 µg (Part 1) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 0.523 Liters | Standard Deviation 0.448 |
| LAS190792 100 µg (Part 1) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 0.536 Liters | Standard Deviation 0.17 |
| LAS190792 200 µg (Part 1) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 0.371 Liters | Standard Deviation 0.333 |
| LAS190792 400 µg (Part 1) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 0.599 Liters | Standard Deviation 0.316 |
| Placebo (Part 1) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 0.029 Liters | Standard Deviation 0.144 |
| LAS190792 100 µg (Part 2) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 1.369 Liters | Standard Deviation 0.505 |
| LAS190792 400 µg (Part 2) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 1.360 Liters | Standard Deviation 0.472 |
| Tiotropium 18 μg | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 1.379 Liters | Standard Deviation 0.502 |
| Indacaterol 150 μg | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 1.361 Liters | Standard Deviation 0.481 |
| Placebo (Part 2) | Change From Baseline in Trough FEV1 (Forced Expiratory Volume in 1 Second) | 1.338 Liters | Standard Deviation 0.506 |
Comparison: Change from baseline to trough FEV1 was analyzed by means of an analysis of covariance (ANCOVA) for cross-over designs with sequence, treatment group and period as fixed effect factors, subject within sequence as random effect, and screening and baseline FEV1 value of each period as covariatesp-value: <0.000195% CI: [0.06, 0.149]ANCOVA
Comparison: Change from baseline to trough FEV1 was analyzed by means of an analysis of covariance (ANCOVA) for cross-over designs with sequence, treatment group and period as fixed effect factors, subject within sequence as random effect, and screening and baseline FEV1 value of each period as covariatesp-value: <0.000195% CI: [0.133, 0.223]ANCOVA
Primary
Subjects With ≥1 Treatment-emergent Adverse Event
Adverse events (AEs) are any unfavorable and unintended medical occurrence during the subject's participation in the study (including deterioration of a pre-existing medical condition, an abnormal value in a laboratory assessment, an ECG abnormality, a 12-lead 24-hour ECG-Holter abnormality, a blood pressure abnormal value, paradoxal bronchospasm or an abnormal finding in the physical examination) and will be coded using the current Medical Dictionary for Regulatory Activities (MedDRA).
Time frame: 30 Days
Population: Safety Population: defined as all randomized subjects who received at least one dose of the investigational product
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LAS190792 5 µg (Part 1) | Subjects With ≥1 Treatment-emergent Adverse Event | 2 Participants |
| LAS190792 20 µg (Part 1) | Subjects With ≥1 Treatment-emergent Adverse Event | 3 Participants |
| LAS190792 50 µg (Part 1) | Subjects With ≥1 Treatment-emergent Adverse Event | 2 Participants |
| LAS190792 100 µg (Part 1) | Subjects With ≥1 Treatment-emergent Adverse Event | 2 Participants |
| LAS190792 200 µg (Part 1) | Subjects With ≥1 Treatment-emergent Adverse Event | 2 Participants |
| LAS190792 400 µg (Part 1) | Subjects With ≥1 Treatment-emergent Adverse Event | 4 Participants |
| Placebo (Part 1) | Subjects With ≥1 Treatment-emergent Adverse Event | 3 Participants |
| LAS190792 100 µg (Part 2) | Subjects With ≥1 Treatment-emergent Adverse Event | 12 Participants |
| LAS190792 400 µg (Part 2) | Subjects With ≥1 Treatment-emergent Adverse Event | 12 Participants |
| Tiotropium 18 μg | Subjects With ≥1 Treatment-emergent Adverse Event | 14 Participants |
| Indacaterol 150 μg | Subjects With ≥1 Treatment-emergent Adverse Event | 21 Participants |
| Placebo (Part 2) | Subjects With ≥1 Treatment-emergent Adverse Event | 15 Participants |
Secondary
Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration
Time frame: Up to 36 hours after investigational product administration
Population: Pharmacokinetic population: defined as all randomized subjects who received at least one dose of investigational product in at least one treatment period and have evaluable PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAS190792 5 µg (Part 1) | Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration | NA pg.h/mL | — |
| LAS190792 20 µg (Part 1) | Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration | 0.106 pg.h/mL | Standard Deviation 0.259 |
| LAS190792 50 µg (Part 1) | Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration | 5.50 pg.h/mL | Standard Deviation 3.53 |
| LAS190792 100 µg (Part 1) | Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration | 20.1 pg.h/mL | Standard Deviation 17.3 |
| LAS190792 200 µg (Part 1) | Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration | 82.7 pg.h/mL | Standard Deviation 43.3 |
| LAS190792 400 µg (Part 1) | Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration | 122 pg.h/mL | Standard Deviation 57.1 |
| Placebo (Part 1) | Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration | 20.5 pg.h/mL | Standard Deviation 15.4 |
| LAS190792 100 µg (Part 2) | Area Under the Concentration-time Curve From Zero to the Time of the Last Measurable Concentration | 127 pg.h/mL | Standard Deviation 67.2 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Up to 36 hours after investigational product administration
Population: Pharmacokinetic population: defined as all randomized subjects who received at least one dose of investigational product in at least one treatment period and have evaluable PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LAS190792 5 µg (Part 1) | Maximum Observed Plasma Concentration (Cmax) | NA pg/mL | — |
| LAS190792 20 µg (Part 1) | Maximum Observed Plasma Concentration (Cmax) | NA pg/mL | — |
| LAS190792 50 µg (Part 1) | Maximum Observed Plasma Concentration (Cmax) | 8.79 pg/mL | Standard Deviation 4.86 |
| LAS190792 100 µg (Part 1) | Maximum Observed Plasma Concentration (Cmax) | 19.5 pg/mL | Standard Deviation 8.45 |
| LAS190792 200 µg (Part 1) | Maximum Observed Plasma Concentration (Cmax) | 43.9 pg/mL | Standard Deviation 16.8 |
| LAS190792 400 µg (Part 1) | Maximum Observed Plasma Concentration (Cmax) | 59.7 pg/mL | Standard Deviation 19.2 |
| Placebo (Part 1) | Maximum Observed Plasma Concentration (Cmax) | 15.4 pg/mL | Standard Deviation 6.39 |
| LAS190792 100 µg (Part 2) | Maximum Observed Plasma Concentration (Cmax) | 56.2 pg/mL | Standard Deviation 10.1 |
Secondary
Time to Maximum Observed Plasma Concentration (Tmax)
Time frame: Up to 36 hours after investigational product administration
Population: Pharmacokinetic population: defined as all randomized subjects who received at least one dose of investigational product in at least one treatment period and have evaluable PK parameters
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LAS190792 5 µg (Part 1) | Time to Maximum Observed Plasma Concentration (Tmax) | NA Hours |
| LAS190792 20 µg (Part 1) | Time to Maximum Observed Plasma Concentration (Tmax) | NA Hours |
| LAS190792 50 µg (Part 1) | Time to Maximum Observed Plasma Concentration (Tmax) | 0.25 Hours |
| LAS190792 100 µg (Part 1) | Time to Maximum Observed Plasma Concentration (Tmax) | 0.5 Hours |
| LAS190792 200 µg (Part 1) | Time to Maximum Observed Plasma Concentration (Tmax) | 0.375 Hours |
| LAS190792 400 µg (Part 1) | Time to Maximum Observed Plasma Concentration (Tmax) | 0.517 Hours |
| Placebo (Part 1) | Time to Maximum Observed Plasma Concentration (Tmax) | 0.5 Hours |
| LAS190792 100 µg (Part 2) | Time to Maximum Observed Plasma Concentration (Tmax) | 0.517 Hours |