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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-002366-12 | EudraCT Number | EudraCT |
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To investigate the safety, tolerability, pharmacokinetics and the relative bioavailability of BI 1026706
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 BI 1026706 single rising dose part | Experimental | single rising doses of BI 1026706 |
|
| 2 BI 1026706 bioavailability part | Experimental | bioavailability part of BI 1026706 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BI 1026706 Placebo | Drug | Placebo to BI 1026706 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects With Drug Related Adverse Events | Percentage of subjects with drug related adverse events. | From the first dose of study medication upto 15 days after the day of last intake of study medication, upto 32 days for SRD Part and 30 days for BA Part. |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Maximum measured concentration of the analyte in plasma (Cmax). The treated set-SRD Part (TS-SRD) included all 68 subjects from the TS who participated in the SRD Part. The treated set-BA Part (TS-BA) included all 12 subjects from the TS who participated in the BA Part. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) included all subjects of the TS-BA who provided observations under the reference treatment (R1) or test treatment (T1) for at least one of the endpoints Cmax, AUC0-tz, or AUC0-inf,without experiencing emesis at or before two times median tmax and without important protocol violations (PVs) relevant to the statistical evaluation of pharmacokinetic (PK). The same definition applies for the analysis set PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1. |
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Inclusion criteria:
1. healthy male subjects
Exclusion criteria:
1. Any relevant deviation from healthy conditions
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1320.1.1 Boehringer Ingelheim Investigational Site | Ingelheim | Germany |
68 subjects were randomised for single rising dose (SRD) part &12 subjects for bioavailability(BA) part of study.
Subjects were recruited from the volunteers' pool of the Human Pharmacology Centre of Boehringer Ingelheim (BI) Pharma GmbH & Co. KG, Ingelheim, Germany.Only male subjects were included because no data on reproductive toxicology was available.
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| ID | Title | Description |
|---|---|---|
| FG000 | BI 1026706 - Tablet 25 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. |
| FG001 | BI 1026706 - Tablet 50 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. |
| FG002 | BI 1026706 - Tablet 100 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. |
| FG003 | BI 1026706 - Tablet 200 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. |
| FG004 | BI 1026706 - Tablet 400 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. |
| FG005 | BI 1026706 - Solution 10 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. |
| FG006 | BI 1026706 - Solution 100 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition |
| FG007 | BI 1026706 - Solution 200 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. |
| FG008 | BI 1026706 - Solution 400 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. |
| FG009 | Placebo (SRD - Part) | Subjects were treated in the morning with one single oral dose of matching placebo tablet and also matching placebo solution with 240 mL of water under fasted condition. |
| FG010 | R1/T1/R2/T2 (BA - Part) | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100mg film coated tablet (R1) under fasted condition, followed by 100mg film coated tablet (T1) under fed condition, 100 mg drinking solution (R2) under fasting and in the last treatment period with 100 mg drinking solution (T2) under fed condition. There was washout period of 7days between the respective treatments. |
| FG011 | T1/T2/R1/R2 (BA - Part) | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning. First they were treated with 100mg film coated tablet (T1) under fed condition, followed by 100 mg drinking solution (T2) under fed condition, 100mg film coated tablet (R1) under fasted condition and in the last treatment period with 100 mg drinking solution (R2) under fasting condition. There was a washout period of 7days between the respective treatments. |
| FG012 | R2/R1/T2/T1 (BA - Part) | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (R2) under fasting condition, followed by 100mg film coated tablet (R1) under fasted condition,100 mg drinking solution (T2) under fed condition and in the last treatment period with 100mg film coated tablet (T1) under fed condition. There was washout period of 7days between the respective treatments. |
| FG013 | T2/R2/T1/R1 (BA - Part) | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (T2) under fed condition, followed by 100 mg drinking solution (R2) under fasting, 100mg film coated tablet (T1) under fed condition and in the last treatment period with 100mg film coated tablet (R1) under fasted condition. There was washout period of 7days between the respective treatments. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | BI 1026706 - Tablet 25 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. |
| BG001 | BI 1026706 - Tablet 50 mg (SRD - Part) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects With Drug Related Adverse Events | Percentage of subjects with drug related adverse events. | The treated set (TS) included all subjects who were documented to have taken at least one dose of study medication. | Posted | Number | Percentage of participants | From the first dose of study medication upto 15 days after the day of last intake of study medication, upto 32 days for SRD Part and 30 days for BA Part. |
|
From the first dose of study medication upto 15 days after the day of last intake of study medication, upto 32 days for SRD Part and 30 days for BA Part.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BI 1026706 - Tablet 25 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 25 mg film coated tablet with 240 mL of water under fasted condition. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear discomfort | Ear and labyrinth disorders | 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| BI 1026706 |
| Drug |
different dose formulations |
|
| -2.0 hours (h) before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
| Tmax (Time From Dosing to Maximum Measured Concentration) | Time from dosing to maximum measured concentration (tmax). | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
| AUC0-inf | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
| AUC0- tz | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0- tz). | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
| t1/2 (Terminal Half-life of the Analyte in Plasma) | Terminal half-life of the analyte in plasma (t1/2). | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
| f t1-t2 (SRD-Part) | Fraction of analyte eliminated in urine from the time point t1 (0h) to time point t2 (72h) (f t1-t2). | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours |
Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition.
| BG002 | BI 1026706 - Tablet 100 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. |
| BG003 | BI 1026706 - Tablet 200 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. |
| BG004 | BI 1026706 - Tablet 400 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. |
| BG005 | BI 1026706 - Solution 10 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. |
| BG006 | BI 1026706 - Solution 100 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition |
| BG007 | BI 1026706 - Solution 200 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. |
| BG008 | BI 1026706 - Solution 400 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. |
| BG009 | Placebo (SRD - Part) | Subjects were treated in the morning with one single oral dose of matching placebo tablet and also matching placebo solution with 240 mL of water under fasted condition. |
| BG010 | R1/T1/R2/T2 (BA - Part) | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100mg film coated tablet (R1) under fasted condition, followed by 100mg film coated tablet (T1) under fed condition, 100 mg drinking solution (R2) under fasting and in the last treatment period with 100 mg drinking solution (T2) under fed condition. There was washout period of 7days between the respective treatments. |
| BG011 | T1/T2/R1/R2 (BA - Part) | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning. First they were treated with 100mg film coated tablet (T1) under fed condition, followed by 100 mg drinking solution (T2) under fed condition, 100mg film coated tablet (R1) under fasted condition and in the last treatment period with 100 mg drinking solution (R2) under fasting condition. There was a washout period of 7days between the respective treatments. |
| BG012 | R2/R1/T2/T1 (BA - Part) | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (R2) under fasting condition, followed by 100mg film coated tablet (R1) under fasted condition,100 mg drinking solution (T2) under fed condition and in the last treatment period with 100mg film coated tablet (T1) under fed condition. There was washout period of 7days between the respective treatments. |
| BG013 | T2/R2/T1/R1 (BA - Part) | Subjects were treated in each of the 4 treatment periods with one single oral dose in the morning, First they were treated with 100 mg drinking solution (T2) under fed condition, followed by 100 mg drinking solution (R2) under fasting, 100mg film coated tablet (T1) under fed condition and in the last treatment period with 100mg film coated tablet (R1) under fasted condition. There was washout period of 7days between the respective treatments. |
| BG014 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition.
| OG002 | BI 1026706 - Tablet 100 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. |
| OG003 | BI 1026706 - Tablet 200 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. |
| OG004 | BI 1026706 - Tablet 400 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. |
| OG005 | BI 1026706 - Solution 10 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. |
| OG006 | BI 1026706 - Solution 100 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition |
| OG007 | BI 1026706 - Solution 200 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. |
| OG008 | BI 1026706 - Solution 400 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. |
| OG009 | Placebo (SRD - Part) | Subjects were treated in the morning with one single oral dose of matching placebo tablet and also matching placebo solution with 240 mL of water under fasted condition. |
| OG010 | BI 1026706 - Solution 100 mg Fasted (R2) | Subjects were treated with 100 mg drinking solution (R2) under fasting condition. |
| OG011 | BI 1026706 - 100 mg Solution Fed (T2) | Subjects were treated with 100 mg drinking solution (T2) under fed condition. |
| OG012 | BI 1026706 - Tablet 100 mg Fasted (R1) | Subjects were treated with 100mg film coated tablet (R1) under fasted condition. |
| OG013 | BI 1026706 - Tablet 100 mg Fed (T1) | Subjects were treated with 100mg film coated tablet (T1) under fed condition. |
|
|
| Secondary | Cmax | Maximum measured concentration of the analyte in plasma (Cmax). The treated set-SRD Part (TS-SRD) included all 68 subjects from the TS who participated in the SRD Part. The treated set-BA Part (TS-BA) included all 12 subjects from the TS who participated in the BA Part. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) included all subjects of the TS-BA who provided observations under the reference treatment (R1) or test treatment (T1) for at least one of the endpoints Cmax, AUC0-tz, or AUC0-inf,without experiencing emesis at or before two times median tmax and without important protocol violations (PVs) relevant to the statistical evaluation of pharmacokinetic (PK). The same definition applies for the analysis set PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1. | TS-SRD, TS-BA, PPS-DP, PPS-BA-T1-R1, PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1 | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomoles Per Litre (nmol/L) | -2.0 hours (h) before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
|
|
|
|
| Secondary | Tmax (Time From Dosing to Maximum Measured Concentration) | Time from dosing to maximum measured concentration (tmax). | The treated set-SRD Part (TS-SRD) included all 68 subjects from the TS who participated in the SRD Part. The treated set-BA Part (TS-BA) included all 12 subjects from the TS who participated in the BA Part. | Posted | Median | Full Range | hours | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
|
|
|
| Secondary | AUC0-inf | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf). | TS-SRD, TS-BA, PPS-DP, PPS-BA-T1-R1, PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1 | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
|
|
|
|
| Secondary | AUC0- tz | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0- tz). | TS-SRD, TS-BA, PPS-DP, PPS-BA-T1-R1, PPS-BA-T2-R2, PPS-BA-R2-R1 and PPS-BA-T2-T1 | Posted | Geometric Mean | Geometric Coefficient of Variation | nmol*h/L | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
|
|
|
|
| Secondary | t1/2 (Terminal Half-life of the Analyte in Plasma) | Terminal half-life of the analyte in plasma (t1/2). | TS-SRD and TS-BA | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | -2.0h before dosing and 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after dosing |
|
|
|
| Secondary | f t1-t2 (SRD-Part) | Fraction of analyte eliminated in urine from the time point t1 (0h) to time point t2 (72h) (f t1-t2). | TS-SRD | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage | 0-4, 4-8, 8-12, 12-24, 24-48, 48-72 hours |
|
|
|
| 0 |
| 6 |
| 1 |
| 6 |
| EG001 | BI 1026706 - Tablet 50 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 50 mg (2x25 mg) film coated tablet with 240 mL of water under fasted condition. | 0 | 6 | 5 | 6 |
| EG002 | BI 1026706 - Tablet 100 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 100 mg film coated tablet with 240 mL of water under fasted condition. | 0 | 6 | 3 | 6 |
| EG003 | BI 1026706 - Tablet 200 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 200 mg (2x100 mg) film coated tablet with 240 mL of water under fasted condition. | 0 | 6 | 2 | 6 |
| EG004 | BI 1026706 - Tablet 400 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 400 mg (4x100 mg) film coated tablet with 240 mL of water under fasted condition. | 0 | 4 | 2 | 4 |
| EG005 | BI 1026706 - Solution 10 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 10 mg solution under fasted condition. | 0 | 6 | 3 | 6 |
| EG006 | BI 1026706 - Solution 100 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 100 mg solution under fasted condition. | 0 | 5 | 2 | 5 |
| EG007 | BI 1026706 - Solution 200 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 200 mg solution under fasted condition. | 0 | 6 | 1 | 6 |
| EG008 | BI 1026706 - Solution 400 mg (SRD - Part) | Subjects were treated in the morning with one single oral dose of 400 mg solution under fasted condition. | 0 | 5 | 4 | 5 |
| EG009 | Placebo (SRD - Part) | Subjects were treated in the morning with one single oral dose of matching placebo tablet and also matching placebo solution with 240 mL of water under fasted condition. | 0 | 18 | 8 | 18 |
| EG010 | BI 1026706 - Solution 100 mg Fasted (R2) | Subjects were treated with 100 mg drinking solution (R2) under fasting condition. | 0 | 11 | 3 | 11 |
| EG011 | BI 1026706 - 100 mg Solution Fed (T2) | Subjects were treated with 100 mg drinking solution (T2) under fed condition. | 0 | 12 | 3 | 12 |
| EG012 | BI 1026706 - Tablet 100 mg Fasted (R1) | Subjects were treated with 100mg film coated tablet (R1) under fasted condition. | 0 | 12 | 6 | 12 |
| EG013 | BI 1026706 - Tablet 100 mg Fed (T1) | Subjects were treated with 100mg film coated tablet (T1) under fed condition. | 0 | 10 | 5 | 10 |
| Ear pain | Ear and labyrinth disorders | 16.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | 16.0 | Systematic Assessment |
|
| Application site haematoma | General disorders | 16.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | 16.0 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | 16.0 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | 16.0 | Systematic Assessment |
|
| Heart rate increased | Investigations | 16.0 | Systematic Assessment |
|
| Platelet count increased | Investigations | 16.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | 16.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | 16.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 16.0 | Systematic Assessment |
|
| Tendon pain | Musculoskeletal and connective tissue disorders | 16.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | 16.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | 16.0 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | 16.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | 16.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | 16.0 | Systematic Assessment |
|
| Dry throat | Respiratory, thoracic and mediastinal disorders | 16.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 16.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 16.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 16.0 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | 16.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | 16.0 | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | 16.0 | Systematic Assessment |
|
Not provided
Not provided
Not provided
| Superiority or Other |
| This was non confirmatory testing (Single dose). Dose proportionality of solution for Cmax was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK. | Slope | 0.9341 | 2-Sided | 95 | 0.8277 | 1.0405 | Dose proportionality was explored using the power model (ANCOVA). The perfect dose proportionality would correspond to a slope β of 1. PK endpoints on the log-transformed scale. | Superiority or Other |
| Relative bioavailability comparison Tab. fed (T1): Tab. fasted (R1) for Cmax. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) was used. | gMean ratio | 112.74 | 2-Sided | 90 | 95.579 | 132.993 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |
| Relative bioavailability comparison Sol. fed (T2) : Sol. fasted (R2) for Cmax. The per protocol set for the evaluation of relative bioavailability of T2 vs R2 (PPS-BA-T2-R2) was used. | gMean ratio | 52.66 | 2-Sided | 90 | 40.488 | 68.499 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |
| Relative bioavailability comparison Sol. fasted (R2): Tab. fasted (R1) for Cmax. The per protocol set for the evaluation of relative bioavailability of R2 vs R1 (PPS-BA-R2-R1) was used. | gMean ratio | 239.63 | 2-Sided | 90 | 197.445 | 290.830 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |
| Relative bioavailability comparison Sol. fed (T2): Tab. fed (T1) for Cmax. The per protocol set for the evaluation of relative bioavailability of T2 vs T1 (PPS-BA-T2-T1) was used. | gMean ratio | 105.47 | 2-Sided | 90 | 85.427 | 130.208 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |
| Superiority or Other |
| This was non confirmatory testing (Single dose).Dose proportionality of solution for AUC0-inf was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK. | Slope | 0.9149 | 2-Sided | 95 | 0.8059 | 1.0239 | Dose proportionality was explored using the power model (ANCOVA). The perfect dose proportionality would correspond to a slope β of 1. PK endpoints on the log-transformed scale. | Superiority or Other |
| Relative bioavailability comparison Tab. fed (T1): Tab. fasted (R1) for AUC0-inf. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) was used. | gMean Ratio | 86.61 | 2-Sided | 90 | 76.529 | 98.029 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |
| Relative bioavailability comparison Sol. fed (T2) : Sol. fasted (R2) for AUC0-inf.The per protocol set for the evaluation of relative bioavailability of T2 vs R2 (PPS-BA-T2-R2) was used. | gMean ratio | 74.44 | 2-Sided | 90 | 66.322 | 83.562 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |
| Relative bioavailability comparison Sol. fasted (R2): Tab. fasted (R1) for AUC0-inf.The per protocol set for the evaluation of relative bioavailability of R2 vs R1 (PPS-BA-R2-R1) was used. | gMean ratio | 137.25 | 2-Sided | 90 | 119.708 | 157.353 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |
| Relative bioavailability comparison Sol. fed (T2): Tab. fed (T1) for AUC0-inf.The per protocol set for the evaluation of relative bioavailability of T2 vs T1 (PPS-BA-T2-T1) was used. | gMean ratio | 116.48 | 2-Sided | 90 | 111.462 | 121.724 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |
| Superiority or Other |
| This was non confirmatory testing (Single dose). Dose proportionality of solution for AUC0-tz was analysed. The per protocol set for the evaluation of dose proportionality (PPS-DP) was used. This set included all subjects of the TS-SRD who provided at least one observation for at least one of the endpoints Cmax, AUC0-tz, AUC0-∞, or Aet1-t2, without experiencing emesis at or before 2 times median tmax and without important PVs relevant to the statistical evaluation of PK. | Slope | 0.9307 | 2-Sided | 95 | 0.8187 | 1.0426 | Dose proportionality was explored using the power model (ANCOVA). The perfect dose proportionality would correspond to a slope β of 1. | Superiority or Other |
| Relative bioavailability comparison Tab. fed (T1) : Tab. fasted (R1) for AUC 0-tz. The per protocol set for the evaluation of relative bioavailability of T1 vs R1 (PPS-BA-T1-R1) was used. | gMean Ratio | 86.16 | 2-Sided | 90 | 75.735 | 98.027 | Adjusted geometric mean (gMean) ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean) |
| Relative bioavailability comparison Sol. fed (T2) : Sol. fasted (R2) for AUC 0-tz.The per protocol set for the evaluation of relative bioavailability of T2 vs R2 (PPS-BA-T2-R2) was used. | gMean ratio | 74.42 | 2-Sided | 90 | 65.979 | 83.941 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean) |
| Relative bioavailability comparison Sol. fasted (R2): Tab. fasted (R1) for AUC 0-tz.The per protocol set for the evaluation of relative bioavailability of R2 vs R1(PPS-BA-R2-R1) was used. | gMean ratio | 137.20 | 2-Sided | 90 | 119.611 | 157.374 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |
| Relative bioavailability comparison Sol. fed (T2): Tab. fed (T1) for AUC 0-tz.The per protocol set for the evaluation of relative bioavailability of T2 vs T1 (PPS-BA-T2-T1) was used. | gMean ratio | 116.83 | 2-Sided | 90 | 111.814 | 122.079 | Adjusted gMean ratio. | Non-Inferiority or Equivalence | The pharmacokinetic parameters were log transformed (natural logarithm) prior to fitting the ANOVA model. The difference between the expected means of the 2 treatments of interest for each pairwise comparison were estimated by the difference in the corresponding Least Square Means (point estimate) and two-sided 90% confidence intervals based on the t-distribution were computed. These quantities were then back-transformed to the original scale to give the point estimator (geometric mean). |