Cystic Fibrosis
Conditions
Brief summary
The objective of this study is to investigate the safety, tolerability, and pharmacokinetics of BI 443651 in male and female healthy volunteers and subjects with Cystic Fibrosis (CF).
Interventions
DRUGBI 443651
twice daily
DRUGPlacebo
twice daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy volunteers: * Signed informed consent * Healthy male or female subjects * \- Women of childbearing potential (WOCBP) should only be dosed after a confirmed menstrual period and/or with a progesterone level at Day -5 to Day -3 that demonstrates a dip from baseline, indicating a menstrual bleed prior to dosing. * Age of 18 to 55 years (incl.) * Body mass index (BMI) of 18.5 to 32.0 kg/m2 (incl.) * Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) of equal or greater than 80% of predicted normal, at screening and prior to randomisation Cystic Fibrosis (Cross over part): * Signed informed consent * Males or females with a documented diagnosis of cystic fibrosis * Women of childbearing potential (WOCBP) should only be dosed after a confirmed menstrual period and/or with a progesterone level at Day -5 to Day -3, that demonstrates a dip from baseline, indicating a menstrual bleed prior to dosing. For CF subjects of child bearing potential this must confirmed prior to second treatment period. * Age 18 to 55 years (each inclusive) * BMI of 18 to 32.0 kg/m2 (incl.) * Pre-bronchodilator FEV1 \>/= to 70% of predicted normal at screening and prior to randomisation * Clinical stability as defined by no evidence of acute upper or lower respiratory tract infection; no pulmonary exacerbation requiring use of i.v. / oral / inhaled antibiotics, or oral corticosteroids; no change in pulmonary disease therapy; if on cycling antibiotics, these must be initiated within 2 weeks prior to randomisation; no acute (serious or non-serious) illness not related to cystic fibrosis; no infection with an organism associated with more rapid decline in pulmonary function (eg, Burkholderia cenocepacia, B dolosa, or Mycobacterium abscessus). * Able to perform technically acceptable pulmonary functions test (PFTs) * Further inclusion criteria apply.
Exclusion criteria
* Any evidence of a concomitant disease judged as clinically relevant by the investigator including gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, dermatologic, hematologic, neurological and psychiatric, oncological, coagulation or hormonal disorders as determined by medical history, examination, and clinical investigations at screening that may, in the opinion of the investigator, result in any of the following: * Put the subject at risk because of participation in the study. * Influence the results of the study. * Cast doubt on the subject's ability to participate in the study. * Chronic or relevant acute infections. * History of relevant orthostatic hypotension, fainting spells, or blackouts * History of myocardial infarction; history of acute coronary syndrome * History of and/or active life-threatening cardiac arrhythmia, as assessed by the investigator * Major surgery (major according to the investigator's assessment) * History of chronic kidney disease (estimate glomerular filtration rate (EGFR) \<59 mls/min including corrections as per ethnicity) * History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients) * Unsuitable veins for venipuncture (for instance, veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture) as assessed by the investigator * Any finding in the medical examination (including blood pressure (BP), pulse rate (PR) or electrocardiogram (ECG) is deviating from normal and judged as clinically relevant by the investigator * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance, specifically volunteers with serum potassium \> upper limit of normal should be excluded; Safety laboratory screening and Day -7 to Day -3, evaluation can be repeated twice during screening. * For healthy volunteers, repeated measurement (i.e. \> 2 measurements) of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg. Volunteers will be excluded with a pulse rate outside the range of 45 to 90 bpm. * A marked baseline prolongation of mean QT/QTcF interval (such as QTcF intervals that are repeatedly greater than 450 ms in males or repeatedly greater than 470 ms in females) or any other relevant ECG finding at screening or prior to randomisation * A history of additional risk factors for Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome). * Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial or that might prolong the QT/QTcF interval * Intake of drugs with a long half-life (more than 24hrs) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication unless this is allowed medications. * CF subjects treated with non-permitted concomitant medication. Specifically medications causing changes in serum potassium are restricted * Current or previous participation in another interventional trial, including where an investigational drug has been or will be administered within 60 days or 5 half-lives (whichever is longer) prior to screening * For healthy volunteers and CF subjects: current smokers or ex-smokers of less than 12 months and/or with a pack year history of more than 5 years * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2 | Up to 44 days (for Part 1) or 51 days (for Part 2) (Please check the measure description for detailed timeframe) | Percentage of participants with treatment-emergent adverse events (TEAE) over the treatment period in Part 1 and Part 2. For Part 1: From the first dose of study medication up to 30 days after the day of last intake of study medication, up to 44 days. For Part 2: From the first dose of study medication up to 30 days after the day of last intake of study medication, up to 51 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1 | Day 1 and Day 7 (Please check the measure description for detailed timeframe) | Maximum measured concentration of the BI 443651 in plasma after the administration of the first dose (Cmax) on day 1 and over the time interval from 0 to 12 h after the 13th dose (Cmax,13) on day 7, in Part 1. Pharmacokinetic samples were collected at 00:15 hours:minutes (h:m) pre-dose and at 00:15, 00:30, 00:45, 1:00, 2:00, 4:00, 6:00, 8:00 and 11:45 h:m after first drug administration on day 1 (for Cmax) and after last drug administration on day 7 (for Cmax,13). |
| Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1 | Day 1 and Day 7 (Please check the measure description for detailed timeframe) | Area under the concentration-time curve of the BI 443651 in plasma over the time interval from 0 to 12 hours (h) after the administration of the first dose (AUC0-12) on day 1 and after the 13th dose (AUC0-12,13) on day 7 in Part 1. Pharmacokinetic samples were collected at 00:15 h:m pre-dose and at 00:15, 00:30, 00:45, 1:00, 2:00, 4:00, 6:00, 8:00 and 11:45 h:m after first drug administration on day 1 (for AUC0-12) and after last drug administration on day 7 (for AUC0-12,13). |
Countries
Germany, United Kingdom
Participant flow
Recruitment details
The trial was conducted in 2 parts. The first part was a multiple rising dose (MRD) trial in healthy participants. The second part followed a cross-over design with respect to placebo and BI 443651 treatment in participants with cystic fibrosis. Both parts were randomised, placebo-controlled, and double-blinded.
Pre-assignment details
All participants were screened for eligibility to participate in the trial. Participants attended specialist sites which would then ensure that they (all participants) met all inclusion/exclusion criteria. Participants were not to be randomized to trial treatment if any one of the specific entry criteria were not met.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching BI 443651 Healthy participants were treated with placebo matching to BI 443651 via Respimat® inhaler twice daily for 6.5 days in Part 1. | 8 |
| BI 443651 100 Microgram (μg) Healthy participants were treated with BI 443651 100 μg dose via Respimat® inhaler twice daily for 6.5 days in Part 1. | 8 |
| BI 443651 400 μg Healthy participants were treated with BI 443651 400 μg dose via Respimat® inhaler twice daily for 6.5 days in Part 1. | 8 |
| BI 443651 1200 μg Healthy participants were treated with BI 443651 1200 μg dose via Respimat® inhaler twice daily for 6.5 days in Part 1. | 8 |
| BI 443651 1800 μg Healthy participants were treated with BI 443651 1800 μg dose via Respimat® inhaler twice daily for 6.5 days in Part 1. | 8 |
| BI 443651 600 μg/ Placebo Matching BI 443651 Participants suffering from cystic fibrosis were treated with 600 μg BI 443651 dose in period 1 and followed by placebo matching to BI 443651 in period 2, both administered via Respimat® inhaler twice daily for 13.5 days treatment periods separated by a wash-out period of at least 30 days between drug administrations in Part 2. | 12 |
| Placebo Matching BI 443651/ BI 443651 600 μg Participants suffering from cystic fibrosis were treated with placebo matching to BI 443651 in period 1 and followed by 600 μg BI 443651 dose in period 2, both administered via Respimat® inhaler twice daily for 13.5 days treatment periods separated by a wash-out period of at least 30 days between drug administrations in Part 2. | 12 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (Part 1 and Part 2) | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (Part 1 and Part 2) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 2 (Part 2 Only) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Wash-out Period (Part 2 Only) | Reason not listed | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Wash-out Period (Part 2 Only) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo Matching BI 443651 | BI 443651 100 Microgram (μg) | BI 443651 400 μg | BI 443651 1200 μg | BI 443651 1800 μg | BI 443651 600 μg/ Placebo Matching BI 443651 | Placebo Matching BI 443651/ BI 443651 600 μg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 36.8 Years STANDARD_DEVIATION 7.9 | 39.1 Years STANDARD_DEVIATION 10.2 | 38.9 Years STANDARD_DEVIATION 9.4 | 32.1 Years STANDARD_DEVIATION 8.1 | 41.1 Years STANDARD_DEVIATION 10.4 | 38.3 Years STANDARD_DEVIATION 12.4 | 34.0 Years STANDARD_DEVIATION 8.1 | 37.1 Years STANDARD_DEVIATION 9.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 12 Participants | 12 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 7 Participants | 5 Participants | 8 Participants | 12 Participants | 11 Participants | 56 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 9 Participants | 7 Participants | 56 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 24 | 0 / 22 |
| other Total, other adverse events | 3 / 8 | 5 / 8 | 7 / 8 | 8 / 8 | 7 / 8 | 8 / 24 | 9 / 22 |
| serious Total, serious adverse events | 0 / 8 | 1 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 1 / 24 | 0 / 22 |
Outcome results
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2
Percentage of participants with treatment-emergent adverse events (TEAE) over the treatment period in Part 1 and Part 2. For Part 1: From the first dose of study medication up to 30 days after the day of last intake of study medication, up to 44 days. For Part 2: From the first dose of study medication up to 30 days after the day of last intake of study medication, up to 51 days.
Time frame: Up to 44 days (for Part 1) or 51 days (for Part 2) (Please check the measure description for detailed timeframe)
Population: TS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo Matching BI 443651 | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2 | 37.5 Percentage of participants (%) |
| BI 443651 100 Microgram (μg) | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2 | 62.5 Percentage of participants (%) |
| BI 443651 400 μg | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2 | 87.5 Percentage of participants (%) |
| BI 443651 1200 μg | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2 | 100.0 Percentage of participants (%) |
| BI 443651 1800 μg | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2 | 87.5 Percentage of participants (%) |
| Placebo Matching BI 443651 600 μg | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2 | 58.3 Percentage of participants (%) |
| BI 443651 600 μg | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) Over the Treatment Period in Part 1 and Part 2 | 59.1 Percentage of participants (%) |
Secondary
Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1
Area under the concentration-time curve of the BI 443651 in plasma over the time interval from 0 to 12 hours (h) after the administration of the first dose (AUC0-12) on day 1 and after the 13th dose (AUC0-12,13) on day 7 in Part 1. Pharmacokinetic samples were collected at 00:15 h:m pre-dose and at 00:15, 00:30, 00:45, 1:00, 2:00, 4:00, 6:00, 8:00 and 11:45 h:m after first drug administration on day 1 (for AUC0-12) and after last drug administration on day 7 (for AUC0-12,13).
Time frame: Day 1 and Day 7 (Please check the measure description for detailed timeframe)
Population: PKS
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Matching BI 443651 | Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1 | AUC0-12 | 409 pmol*h/L | Geometric Coefficient of Variation 50.5 |
| Placebo Matching BI 443651 | Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1 | AUC0-12,13 | 868 pmol*h/L | Geometric Coefficient of Variation 35.3 |
| BI 443651 100 Microgram (μg) | Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1 | AUC0-12,13 | 2260 pmol*h/L | Geometric Coefficient of Variation 54 |
| BI 443651 100 Microgram (μg) | Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1 | AUC0-12 | 1980 pmol*h/L | Geometric Coefficient of Variation 47.7 |
| BI 443651 400 μg | Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1 | AUC0-12 | 9150 pmol*h/L | Geometric Coefficient of Variation 59.6 |
| BI 443651 400 μg | Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1 | AUC0-12,13 | 12200 pmol*h/L | Geometric Coefficient of Variation 37.6 |
| BI 443651 1200 μg | Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1 | AUC0-12 | 16200 pmol*h/L | Geometric Coefficient of Variation 43.9 |
| BI 443651 1200 μg | Area Under the Concentration-time Curve of the BI 443651 in Plasma Over the Time Interval From 0 to 12 Hours After the Administration of the First Dose (AUC0-12) on Day 1 and After the 13th Dose (AUC0-12,13) on Day 7 in Part 1 | AUC0-12,13 | 18400 pmol*h/L | Geometric Coefficient of Variation 54.6 |
Comparison: AUC0-12. The basic model used for the investigation of dose proportionality was a power model (regression model applied to log-transformed data) that described the functional relationship between the dose and PK endpoints.95% CI: [1.1231, 1.4255]
Comparison: AUC0-12,13. The basic model used for the investigation of dose proportionality was a power model (regression model applied to log-transformed data) that described the functional relationship between the dose and PK endpoints.95% CI: [0.9296, 1.2551]
Secondary
Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1
Maximum measured concentration of the BI 443651 in plasma after the administration of the first dose (Cmax) on day 1 and over the time interval from 0 to 12 h after the 13th dose (Cmax,13) on day 7, in Part 1. Pharmacokinetic samples were collected at 00:15 hours:minutes (h:m) pre-dose and at 00:15, 00:30, 00:45, 1:00, 2:00, 4:00, 6:00, 8:00 and 11:45 h:m after first drug administration on day 1 (for Cmax) and after last drug administration on day 7 (for Cmax,13).
Time frame: Day 1 and Day 7 (Please check the measure description for detailed timeframe)
Population: Pharmacokinetic (PK) set (PKS): The PKS included all subjects in the TS who provided at least 1 PK parameter that was not excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Matching BI 443651 | Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1 | Cmax | 158 picomole (pmol)/Litre (L) | Geometric Coefficient of Variation 60.8 |
| Placebo Matching BI 443651 | Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1 | Cmax,13 | 250 picomole (pmol)/Litre (L) | Geometric Coefficient of Variation 31.9 |
| BI 443651 100 Microgram (μg) | Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1 | Cmax,13 | 745 picomole (pmol)/Litre (L) | Geometric Coefficient of Variation 70.3 |
| BI 443651 100 Microgram (μg) | Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1 | Cmax | 782 picomole (pmol)/Litre (L) | Geometric Coefficient of Variation 46.8 |
| BI 443651 400 μg | Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1 | Cmax | 3400 picomole (pmol)/Litre (L) | Geometric Coefficient of Variation 64.7 |
| BI 443651 400 μg | Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1 | Cmax,13 | 4000 picomole (pmol)/Litre (L) | Geometric Coefficient of Variation 27.2 |
| BI 443651 1200 μg | Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1 | Cmax | 6320 picomole (pmol)/Litre (L) | Geometric Coefficient of Variation 48.2 |
| BI 443651 1200 μg | Maximum Measured Concentration of the BI 443651 in Plasma After the Administration of the First Dose (Cmax) on Day 1 and Over the Time Interval From 0 to 12 h After the 13th Dose (Cmax,13) on Day 7, in Part 1 | Cmax,13 | 6060 picomole (pmol)/Litre (L) | Geometric Coefficient of Variation 70.6 |
Comparison: Cmax. The basic model used for the investigation of dose proportionality was a power model (regression model applied to log-transformed data) that described the functional relationship between the dose and PK endpoints.95% CI: [1.1067, 1.4343]
Comparison: Cmax,13. The basic model used for the investigation of dose proportionality was a power model (regression model applied to log-transformed data) that described the functional relationship between the dose and PK endpoints.95% CI: [0.9598, 1.3123]