Bladder, Neurogenic
Conditions
Keywords
tamsulosin, pediatric, neurogenic bladder
Brief summary
Aims of this study is to characterize the pharmacokinetic/pharmacodynamic profile and evaluate the safety, efficacy and tolerability, of tamsulosin hydrochloride as treatment in children with a neuropathic bladder, over the course of 12 months of active treatment.
Interventions
oral
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Neuropathic bladder secondary to known neurological disorder * Elevated detrusor leak point pressures (LPP) ≥40 cm H2O confirmed by two measurements at baseline
Exclusion criteria
* Clinically significant abnormalities as determined by the investigator * A history of relevant orthostatic hypotension, fainting spells or blackouts
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of LPP Responders for Group D-Denovo and Group D-527.51 Rollover | Group D-Denovo: Week 52. Group D-527.51 Rollover: Week 1, Week 2, Week 3 and Week 4 prior to dose administration and Week9 (optional), Week 13 (additional), Week 26 (optional) and Week 52 after drug administration. | Group D-Denovo: Leak point pressure (LPP) Response at(response defined as a subject who achieves an LPP pressure \<40 cm H2O) at the end of treatment based on two confirmatory values. Group D-527.51 Rollover: Leak point pressure (LPP) Response at (response defined as a subject who achieves an LPP pressure \<40 cm H2O) last value of the treatment based on two confirmatory values. The last value on treatment included any final value prior to discontinuation of treatment, regardless of the length of treatment. Detrusor leak point pressure (LPP) recorded in cm H2O which was obtained using a standard urodynamic technique, a cystometrogram. Descriptive statistics were used to assess this endpoint. This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, so results of these two groups are provided. |
| Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 1 (Visit 3) , Week 2 (Visit 4) , Week 3 (Visit 5) and Week 4 (Visit 6) prior to dose administration and Week 9 (Visit 7) (optional), Week 13 (Visit 8) (additional), Week 26 (Visit 9) (optional) and Week 52 (Visit 11) after drug administration. | Number of Leak point pressure (LPP) Responders at each visit (week) over time (classified by last value on treatment). Due to the early termination of the study, most of the LPP assessments were conducted within Weeks 1-9 of treatment. Summary of LPP response rates provided over time.The subjects are classified according to the treatment they were receiving at the last value on treatment. Therefore, no assumptions can be made regarding what dose they were receiving at a particular time point. LD: Low Dose, MD: Medium Dose and HD: High Dose This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in LPP for Group D-527.51 Rollover | Baseline and Week 1 | Percent change from baseline in actual detrusor leak point pressure (LPP) by treatment group (subjects are classified according to the treatment they were taking at end of treatment) and Week. Baseline assessments were obtained from trial 527.51 for Group D-527.51 Rollover. The results from Week 1 were reported because there were very few subjects who reported data at subsequent visits due to the termination of the trial. This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided. |
| Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Group D-Denovo: Baseline and Week 52. Group D-527.51 Rollover: Baseline, Week 26 and Week 52. | Response defined as stabilization or improvement of hydroureter measured by renal ultrasound compared to baseline by treatment group (subjects are classified according to the treatment they were taking at Week 52 or end of treatment) at week 52 for Group D-Denovo and (subjects are classified according to the treatment they were taking at the end of treatment) at last value on treatment for Group D-527.51 Rollover. Baseline assessments were obtained from trial 527.51 for Group D-527.51 Rollover. The overall treatment duration was not sufficient to reach any meaningful conclusions regarding improvement or stabilization of hydroureter in the Group D-527.51 Rollover. Hydroureter response is defined as improvement or stabilization based upon the presence or absence of hydroureter at end of treatment compared to baseline. This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, so results of these two groups are provided. |
| Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Group D-Denovo: Baseline and Week 52. Group D-527.51 Rollover: Baseline, Week 26 and Week 52. | Response defined as stabilization or improvement of hydronephrosis measured by renal ultrasound compared to baseline by treatment group (subjects are classified according to the treatment they were taking at Week 52 or end of treatment) at week 52 for Group D-Denovo and (subjects are classified according to the treatment they were taking at the end of treatment) at last value on treatment for Group D-527.51 Rollover. Baseline assessments were obtained from trial 527.51 for Group D-527.51 Rollover. The overall treatment duration was not sufficient to reach any meaningful conclusions regarding improvement or stabilization of hydronephrosis in the Group D-527.51 Rollover. Hydronephrosis response is defined as an improvement or stabilization based upon ultrasound grading at the end of the study. The lower or same grade at end of treatment compared to baseline is considered an improvement or stabilization. |
| LPP Response at Any Time During the Trial for Group D-Denovo and Group D-527.51 Rollover | Week 1 to Week 52 (described study wise in the Description). | Response rates of LPP responders (2 LPP values \< 40 cm H2O) at any time during the trial by treatment group. Timeframe for Group D-Denovo: Low dose: Week 1, 3 & 4 prior to dose and Week 2, 9 & 26 (optional), 13(additional) & 52 post dose. Medium dose: Week 1, 2 & 4 prior to dose and Week 3, 9(optional), 13(additional), 26 (optional) & 52 post dose. High dose: Week 1, 2 & 3 prior to dose administration and Week 4, 9(optional), 13(additional), 26 (optional) & 52 post dose. Group D-527.51 Rollover: Week 1, 2, 3 & 4 prior to dose and Week 9 &26 (optional),13 (additional) & 52 post dose. This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, so results of these two groups are provided. |
| Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values,Urinalysis,Occurence of Adverse Events & Cognitive Testing for Group D-527.51 Rollover | From first drug administration until 28 days after last study drug administration, upto 395 days | Number of participants with Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse events and Cognitive Testing. Relevant findings or worsening of baseline conditions were reported as adverse events. Below mentioned result are the number of subjects who had the clinical relevant abnormalities for the preferred term 'Hepatic enzyme increased'. This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided. |
| Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | From first drug administration until 28 days after last study drug administration, upto 450 days | Number of participants with Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse events and Cognitive Testing. Relevant findings or worsening of baseline conditions were reported as adverse events. Subjects who experienced orthostatic hypotension during orthostatic testing were reported as adverse events. This Outcome Measure was only pre-specified for Group D-Denovo, so results of this group is provided. |
| Vision Testing for Group D-Denovo | Baseline, Week 26 and Week 52. | Number of subjects with a change from baseline in visual acuity by treatment group (subjects are classified according to the treatment they were taking at Week 52 or end of treatment). They were analysed based on the below mentioned category in both the Eyes: 1) No Change 2) Decrease in visual acuity 3) Increase in visual acuity 4) Missing. Missing includes subjects with no baseline exam and subjects with exam scores missing. This Outcome Measure was only pre-specified for Group D-Denovo subjects, so results of this group is provided. |
| Vision Testing for Group D-527.51 Rollover | Baseline and Week 52 | Number of subjects with a change from baseline in visual acuity by treatment group (subjects are classified according to the treatment they were taking at end of treatment). They were analysed based on the below mentioned category in both the Eyes: 1) No Change 2) Decrease in visual acuity 3) Increase in visual acuity 4) Missing. Missing includes subjects with no baseline exam and subjects with exam scores missing. This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided. |
| Cmax,1 | -0.25h prior to dose and 2h, 4h, 6h and 8h after the drug administration. | Maximum measured concentration of the analyte in plasma following the first dose, Cmax,1. This Outcome Measure was only pre-specified for PK Study- single dose group subjects, so results of this group is provided. |
| Tmax, 1 | -0.25h prior to dose and 2h, 4h, 6h and 8h after the drug administration. | Time from dosing to maximum measured concentration of the analyte in plasma after administration of the first dose, tmax, 1. This Outcome Measure was only pre-specified for PK Study- single dose group subjects, so results of this group is provided. |
| Cmax, 1 ,DW ,Norm | -0.25h prior to dose and 2h, 4h, 6h and 8h after the drug administration. | Dose- and weight-normalized Cmax,1 (Cmax,1,DW,norm). Weight normalization of Cmax,1 was performed by dividing the respective quantities by the reciprocal of body weight in kg. This Outcome Measure was only pre-specified for PK Study- single dose group subjects, so results of this group is provided. |
| Cpre,ss | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose, Cpre,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| Early Responders Who Maintained Their LPP Below 40 cm H2O During the Study for Group D-Denovo and Group D-527.51 Rollover | Week 1 to Week 52 (Time frame for all weeks are described study wise in the Description). | Early responders who maintained their detrusor leak point pressure (LPP) below 40 cm H2O during the study. Timeframe for Group D-Denovo: Low dose: Week 1, 3 & 4 prior to dose and Week 2, 9 & 26 (optional), 13(additional) & 52 post dose. Medium dose: Week 1, 2 & 4 prior to dose and Week 3, 9(optional), 13(additional), 26 (optional) & 52 post dose. High dose: Week 1, 2 & 3 prior to dose administration and Week 4, 9(optional), 13(additional), 26 (optional) & 52 post dose. Group D-527.51 Rollover: Week 1, 2,3 & 4 prior to dose and Week 9 &26 (optional),13 (additional) & 52 post dose. This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, However this endpoint was not analysed for Group D-527.51 Rollover as very limited data were collected due to early termination of the study & no alternative endpoint was defined in the Group D-527.51 rollover, so only the results for Group D-Denovo is provided. |
| Cmax,ss, DW, Norm | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Dose- and weight-normalized for Cmax,ss, Cmax,ss, DW, norm. Weight normalization of Cmax,ss was performed by dividing the respective quantities by the reciprocal of body weight in kg. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| Cmin,ss | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ, Cmin,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| λz,ss | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Terminal rate constant of the analyte in plasma at steady state, λz,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| Tmax,ss | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Time from last dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ, tmax,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| AUCτ,ss | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ , AUCτ,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| AUCτ ,ss ,DW ,Norm | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Dose- and weight-normalized of AUCτ ,ss ( AUCτ ,ss ,DW ,norm). Weight normalization of AUCτ,ss was performed by dividing the respective quantities by the reciprocal of body weight in kg. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| t1/2,ss | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Terminal half-life of the analyte in plasma at steady state, t1/2,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| MRTpo,ss | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Mean residence time of the analyte in the body at steady state after oral administration,MRTpo,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| CL/F,ss,W,Norm | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Weight-normalized CL/F,ss (apparent clearance of the analyte in the plasma at steady state after extravascular multiple dose administration), CL/F,ss,W,norm. Weight-normalized CL/F,ss was calculated by dividing the respective quantities by body weight in kg. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| Vz/F,ss,W,Norm | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Weight-normalized Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration), Vz/F,ss,W,norm. Weight-normalized VzF,ss was calculated by dividing the respective quantities by body weight in kg. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| RA,Cmax | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | The accumulation ratio was calculated from the patients who were randomised to the low dose group and for whom both parameters at first dose and steady state dose were available. Accumulation ratios of tamsulosin HCl in plasma at steady state after multiple dose administration over a uniform dosing interval τ, expressed as ratio of Cmax at steady state and after single dose. The accumulation ratio RA,Cmax was calculated as: Cmax,ss/Cmax,1. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results from this group is provided. |
| Cmax,ss | -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration. | Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ, Cmax,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided. |
| Change From Baseline in LPP for Group D-527.51 Rollover | Baseline and week 1 | Median change from baseline in detrusor leak point pressure (LPP) by treatment group (subjects are classified according to the treatment they were taking at end of treatment) and week. Baseline assessments were obtained from trial 527.51 for Group D-527.51 Rollover. The results from Week 1 were reported because there were very few subjects who reported data at subsequent visits due to the termination of the trial. This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided. |
Countries
Belgium, Brazil, Canada, Germany, India, Italy, Mexico, Philippines, Russia, South Africa, South Korea, Spain, Ukraine, United States
Participant flow
Recruitment details
This trial has 3 different Data base locks (DBLs) based on 3 separate populations PK/PD, Group D-Denovo & Group D-527.51 Rollover. For population PK/PD the DBL date was 18July2007, Group D-Denovo the DBL date was 23Jan2009 & Group D-527.51 Rollover the DBL date was 11Sep2009.
Pre-assignment details
Three different Clinical trial reports were prepared based on 3 separate populations (PK/PD, Group D-Denovo & Group D-527.51). Group D-Denovo includes patients from PK Phase & additional subjects & Group D-527.51 Rollover includes patients who successfully completed tamsulosin HCl Study 527.51
Participants by arm
| Arm | Count |
|---|---|
| Tamsulosin - Low Dose Level (PK Study) Subjects randomized to low dose level (0.001-0.002 mg/kg) of tamsulosin hydrochloride, dependent on a subject's body weight. In PK study, all subjects were titrated to their randomized dose level that they needed to receive which was based on their weight. Depending on the results of the Leak point pressure (LPP) results, subjects could remain on that dose if it was found to be efficacious or go back to a lower efficacious dose or titrate up in hopes that the higher dose would provide some efficacy. Subjects with body weight of 12.1-25.0 kg received low dose of 0.025 mg qd (once daily), body weight of 25.1-50.0 kg received low dose of 0.05 mg qd and body weight of 50.1-100.0 kg received low dose of 0.1 mg qd by sprinkling the content of the capsule(s) over teaspoon of apple sauce or yogurt taken 30 minutes after breakfast. | 10 |
| Tamsulosin - Medium Dose Level (PK Study) Subjects randomized to medium dose level (0.002-0.004 mg/kg) of tamsulosin hydrochloride, dependent on a subject's body weight. In PK study, all subjects were titrated to their randomized dose level that they needed to receive which was based on their weight. Depending on the results of the LPP results, subjects could remain on that dose if it was found to be efficacious or go back to a lower efficacious dose or titrate up in hopes that the higher dose would provide some efficacy. Subjects with body weight of 12.1-25.0 kg received medium dose of 0.05 mg qd, body weight of 25.1-50.0 kg received medium dose of 0.1 mg qd with and body weight of 50.1-100.0 kg received medium dose of 0.2 mg qd by sprinkling the content of the capsule(s) over teaspoon of apple sauce or yogurt, taken 30 minutes after breakfast. | 10 |
| Tamsulosin - High Dose Level (PK Study) Subjects randomized to high dose level(0.004-0.008mg/kg) of tamsulosin hydrochloride,dependent on a subject's body weight. In PK study,all subjects were titrated to their randomized dose level that they needed to receive which was based on their weight.Depending on the results of the LPP,subjects could remain on that dose if it was found to be efficacious or go back to a lower efficacious dose or titrate up in hopes that the higher dose would provide some efficacy. Subjects with body weight of 12.1-25.0kg received high dose of 0.1mg qd,body weight of 25.1-50.0kg received high dose of 0.2mg qd & body weight of 50.1-100.0kg received high dose of 0.4mg qd by sprinkling the content of the capsule(s) over teaspoon of apple sauce or yogurt taken 30 minutes after breakfast. | 10 |
| Tamsulosin - Low Dose Level (Group D-Denovo) Subjects received low dose level (0.001 - 0.002 mg/kg) of tamsulosin hydrochloride, dependent on a subject's body weight. In Group D-Denovo, all subjects started the study at the low Dose level, with the exception of the children with a body weight between 9 kg and 12 kg (they started at the Medium Dose level), and titrated up to higher dose levels on a weekly basis until an efficacious level was reached. The subjects remained on their efficacious dose level for the remainder of the study. Subjects with body weight of 12.1- 25.0 kg received low dose of 0.025 mg qd, body weight of 25.1-50.0 kg received low dose of 0.05 mg qd and body weight of 50.1-100.0 kg received low dose of 0.1 mg qd by sprinkling the content of the capsule(s) over teaspoon of apple sauce or yogurt taken 30 minutes after breakfast. | 22 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) Subjects who were titrated to medium dose level (0.002-0.004 mg/kg) of tamsulosin hydrochloride, dependent on a subject's body weight. In Group D-Denovo, all subjects started the study at the Low Dose level, with the exception of the children with a body weight between 9 kg and 12 kg (they started at the Medium Dose level), and titrated up to higher dose levels on a weekly basis until an efficacious level was reached. The subjects remained on their efficacious dose level for the remainder of the study. Subjects with body weight of 9.0-12.0 kg received medium dose of 0.025 mg qd as their starting dose, body weight of 12.1-25.0 kg could have titrated to a medium dose of 0.05 mg qd, body weight of 25.1-50.0 kg could have titrated to a medium dose of 0.1 mg qd and body weight of 50.1-100.0 kg could have titrated to a medium dose of 0.2 mg qd by sprinkling the content of the capsule(s) over teaspoon of apple sauce or yogurt, taken 30 minutes after breakfast. | 16 |
| Tamsulosin - High Dose Level (Group D-Denovo) Subjects titrated to high dose level (0.004-0.008 mg/kg) of tamsulosin hydrochloride, once daily dependent on a subject's body weight. In Group D-Denovo, all subjects started the study at the Low Dose level, with the exception of the children with a body weight between 9 kg and 12 kg (they started at the Medium Dose level), and titrated up to higher dose levels on a weekly basis until an efficacious level was reached. The subjects remained on their efficacious dose level for the remainder of the study. Subjects with body weight of 9.0-12.0 kg received high dose of 0.05 mg qd, body weight of 12.1-25.0 kg received high dose of 0.1 mg qd, body weight of 25.1-50.0 kg received high dose of 0.2 mg qd & body weight of 50.1-100.0 kg received high dose of 0.4 mg qd by sprinkling the content of the capsule(s) over teaspoon of apple sauce or yogurt, taken 30 minutes after breakfast. | 19 |
| Tamsulosin - Low Dose Level (Group D-527.51 Rollover) Subjects received low dose level (0.001-0.002 mg/kg) of tamsulosin hydrochloride, once daily dependent on a subject's body weight. In Group D- 527.51 Rollover, once subjects exited the double-blind trial they were rolled over into this trial (527.66). All subjects were to titrate to their efficacious dose. Doses that were available were based on subject's weight. Depending on the LPP results, subjects could remain on that dose if it was found to be efficacious or titrate up in hopes that that the higher doses would provide some efficacy. Subjects with body weight of 12.1-25.0 kg received low dose of 0.025 mg qd, body weight of 25.1-50.0 kg received low dose of 0.05 mg qd and body weight of 50.1-100.0 kg qd received low dose of 0.1 mg qd by sprinkling the content of the capsule(s) over teaspoon of apple sauce or yogurt, taken 30 minutes after breakfast. | 54 |
| Tamsulosin - Medium Dose Level (Group D-527.51 Rollover) Subjects who were to receive medium dose level (0.002-0.004 mg/kg) of tamsulosin hydrochloride, once daily dependent on a subject's body weight. In Group D-527.51 Rollover, once subjects exited the double-blind trial they were rolled over into this trial. All subjects were to titrate to their efficacious dose. Doses that were available were based on subject's weight. Depending on the LPP results, subjects could remain on that dose if it was found to be efficacious or titrate up in hopes that the higher doses would provide some efficacy. Subjects with body weight of 9.0-12.0 kg received medium dose of 0.025 mg qd, body weight of 12.1-25.0 kg received medium dose of 0.05 mg qd, body weight of 25.1-50.0 kg received medium dose of 0.1 mg qd, body weight of 50.1-100.0 kg received medium dose of 0.2 mg qd by sprinkling the content of the capsule(s) over teaspoon of apple sauce or yogurt taken 30 minutes after breakfast. | 13 |
| Tamsulosin - High Dose Level (Group D-527.51 Rollover) Subjects titrated to high dose level (0.004-0.008 mg/kg) of tamsulosin hydrochloride, once daily dependent on a subject's body weight. In Group D-527.51 Rollover, once subjects exited the double-blind trial they were rolled over into this trial. All subjects had to titrate to their efficacious dose. Doses that were available were based on subject's weight. Depending on the LPP results, subjects could remain on that dose if it was found to be efficacious or titrate up in hopes that the higher doses would provide some efficacy. Subjects with body weight of 9.0-12.0 kg received high dose of 0.05 mg, body weight of 12.1-25.0 kg received high dose of 0.1 mg, body weight of 25.1-50.0 kg received high dose of 0.2 mg, body weight of 50.1-100.0 kg received high dose of 0.4 mg by sprinkling the content of the capsule(s) over teaspoon of apple sauce or yogurt taken 30 minutes after breakfast. | 29 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Group D- Denovo & 527.51 Rollover Study | Adverse Event | 0 | 0 | 0 | 2 | 4 | 0 | 0 | 1 | 1 |
| Group D- Denovo & 527.51 Rollover Study | Other reason not defined above | 0 | 0 | 0 | 0 | 0 | 3 | 53 | 11 | 28 |
| Group D- Denovo & 527.51 Rollover Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Group D- Denovo & 527.51 Rollover Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 | 0 |
| PK Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| PK Study | Not treated | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Tamsulosin - Low Dose Level (PK Study) | Tamsulosin - Medium Dose Level (PK Study) | Tamsulosin - High Dose Level (PK Study) | Tamsulosin - Low Dose Level (Group D-Denovo) | Tamsulosin - Medium Dose Level (Group D-Denovo) | Tamsulosin - High Dose Level (Group D-Denovo) | Tamsulosin - Low Dose Level (Group D-527.51 Rollover) | Tamsulosin - Medium Dose Level (Group D-527.51 Rollover) | Tamsulosin - High Dose Level (Group D-527.51 Rollover) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 8.7 years STANDARD_DEVIATION 4.5 | 6.5 years STANDARD_DEVIATION 2.6 | 8.8 years STANDARD_DEVIATION 3.7 | 6.8 years STANDARD_DEVIATION 3.4 | 6.3 years STANDARD_DEVIATION 3.7 | 8.1 years STANDARD_DEVIATION 3.8 | 8.1 years STANDARD_DEVIATION 3.8 | 7.0 years STANDARD_DEVIATION 3.4 | 8.3 years STANDARD_DEVIATION 4.1 | 7.7 years STANDARD_DEVIATION 3.7 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 5 Participants | 12 Participants | 7 Participants | 10 Participants | 21 Participants | 8 Participants | 12 Participants | 83 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 5 Participants | 10 Participants | 9 Participants | 9 Participants | 33 Participants | 5 Participants | 17 Participants | 100 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 10 | 5 / 10 | 3 / 10 | 51 / 82 | 25 / 61 | 33 / 41 | 31 / 93 | 10 / 41 | 9 / 29 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 | 0 / 10 | 2 / 82 | 3 / 61 | 4 / 41 | 1 / 93 | 1 / 41 | 1 / 29 |
Outcome results
Primary
Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover.
Number of Leak point pressure (LPP) Responders at each visit (week) over time (classified by last value on treatment). Due to the early termination of the study, most of the LPP assessments were conducted within Weeks 1-9 of treatment. Summary of LPP response rates provided over time.The subjects are classified according to the treatment they were receiving at the last value on treatment. Therefore, no assumptions can be made regarding what dose they were receiving at a particular time point. LD: Low Dose, MD: Medium Dose and HD: High Dose This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided.
Time frame: Week 1 (Visit 3) , Week 2 (Visit 4) , Week 3 (Visit 5) and Week 4 (Visit 6) prior to dose administration and Week 9 (Visit 7) (optional), Week 13 (Visit 8) (additional), Week 26 (Visit 9) (optional) and Week 52 (Visit 11) after drug administration.
Population: Full analysis set (FAS-LPP)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 1 (N= 40 (LD), 12 (MD), 27 (HD)) | 38 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 2 (N= 2 (LD), 7 (MD), 27 (HD)) | 2 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 3 (N= 3 (LD), 0 (MD), 22 (HD)) | 2 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 4 (N= 1 (LD), 0 (MD), 3 (HD)) | 1 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 9 (N= 7 (LD), 2 (MD), 16 (HD)) | 5 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 13 (N= 4 (LD), 0 (MD), 2 (HD)) | 1 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 26 (N= 2 (LD), 0 (MD), 3 (HD)) | 1 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 52 (N= 1 (LD), 1 (MD), 0 (HD)) | 1 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 3 (N= 3 (LD), 0 (MD), 22 (HD)) | 0 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 26 (N= 2 (LD), 0 (MD), 3 (HD)) | 0 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 4 (N= 1 (LD), 0 (MD), 3 (HD)) | 0 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 9 (N= 7 (LD), 2 (MD), 16 (HD)) | 2 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 13 (N= 4 (LD), 0 (MD), 2 (HD)) | 0 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 1 (N= 40 (LD), 12 (MD), 27 (HD)) | 1 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 2 (N= 2 (LD), 7 (MD), 27 (HD)) | 7 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 52 (N= 1 (LD), 1 (MD), 0 (HD)) | 1 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 3 (N= 3 (LD), 0 (MD), 22 (HD)) | 5 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 2 (N= 2 (LD), 7 (MD), 27 (HD)) | 2 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 1 (N= 40 (LD), 12 (MD), 27 (HD)) | 0 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 4 (N= 1 (LD), 0 (MD), 3 (HD)) | 0 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 26 (N= 2 (LD), 0 (MD), 3 (HD)) | 1 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 13 (N= 4 (LD), 0 (MD), 2 (HD)) | 1 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 9 (N= 7 (LD), 2 (MD), 16 (HD)) | 5 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of LPP Responders at Each Visit Over Time (Classified by Last Value on Treatment) for Group D-527.51 Rollover. | Week 52 (N= 1 (LD), 1 (MD), 0 (HD)) | 0 Participants |
Primary
Percentage of LPP Responders for Group D-Denovo and Group D-527.51 Rollover
Group D-Denovo: Leak point pressure (LPP) Response at(response defined as a subject who achieves an LPP pressure \<40 cm H2O) at the end of treatment based on two confirmatory values. Group D-527.51 Rollover: Leak point pressure (LPP) Response at (response defined as a subject who achieves an LPP pressure \<40 cm H2O) last value of the treatment based on two confirmatory values. The last value on treatment included any final value prior to discontinuation of treatment, regardless of the length of treatment. Detrusor leak point pressure (LPP) recorded in cm H2O which was obtained using a standard urodynamic technique, a cystometrogram. Descriptive statistics were used to assess this endpoint. This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, so results of these two groups are provided.
Time frame: Group D-Denovo: Week 52. Group D-527.51 Rollover: Week 1, Week 2, Week 3 and Week 4 prior to dose administration and Week9 (optional), Week 13 (additional), Week 26 (optional) and Week 52 after drug administration.
Population: Full analysis set (FAS-LPP): This subject set includes all subjects in the Treated set who received one dose of treatment and had one on treatment LPP measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Percentage of LPP Responders for Group D-Denovo and Group D-527.51 Rollover | 73.1 percentage of responders |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Percentage of LPP Responders for Group D-Denovo and Group D-527.51 Rollover | 35.7 percentage of responders |
| Tamsulosin - High Dose Level (Group D-Denovo) | Percentage of LPP Responders for Group D-Denovo and Group D-527.51 Rollover | 26.7 percentage of responders |
| Tamsulosin - Low Dose Level (Group D-527.51 Rollover) | Percentage of LPP Responders for Group D-Denovo and Group D-527.51 Rollover | 67.9 percentage of responders |
| Tamsulosin - Medium Dose Level (Group D-527.51 Rollover) | Percentage of LPP Responders for Group D-Denovo and Group D-527.51 Rollover | 58.3 percentage of responders |
| Tamsulosin - High Dose Level (Group D-527.51 Rollover) | Percentage of LPP Responders for Group D-Denovo and Group D-527.51 Rollover | 20.7 percentage of responders |
Secondary
AUCτ,ss
Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ , AUCτ,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | AUCτ,ss | 35.80 ng*h/mL | Geometric Coefficient of Variation 75.6 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | AUCτ,ss | 68.20 ng*h/mL | Geometric Coefficient of Variation 94.7 |
| Tamsulosin - High Dose Level (Group D-Denovo) | AUCτ,ss | 175.00 ng*h/mL | Geometric Coefficient of Variation 61 |
Comparison: Dose proportionality for AUCτ,ss was explored based on the regression model.95% CI: [0.5934, 1.3666]
Secondary
AUCτ ,ss ,DW ,Norm
Dose- and weight-normalized of AUCτ ,ss ( AUCτ ,ss ,DW ,norm). Weight normalization of AUCτ,ss was performed by dividing the respective quantities by the reciprocal of body weight in kg. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | AUCτ ,ss ,DW ,Norm | 26100 ng*h/mL/mg*kg | Geometric Coefficient of Variation 91.1 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | AUCτ ,ss ,DW ,Norm | 25200 ng*h/mL/mg*kg | Geometric Coefficient of Variation 82.9 |
| Tamsulosin - High Dose Level (Group D-Denovo) | AUCτ ,ss ,DW ,Norm | 27700 ng*h/mL/mg*kg | Geometric Coefficient of Variation 59.1 |
Secondary
Change From Baseline in LPP for Group D-527.51 Rollover
Median change from baseline in detrusor leak point pressure (LPP) by treatment group (subjects are classified according to the treatment they were taking at end of treatment) and week. Baseline assessments were obtained from trial 527.51 for Group D-527.51 Rollover. The results from Week 1 were reported because there were very few subjects who reported data at subsequent visits due to the termination of the trial. This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided.
Time frame: Baseline and week 1
Population: Full analysis set (FAS-LPP)
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Actual (N= 39 (LD), 9 (MD),22 (HD)) | 29.00 cm H2O | Standard Deviation 8.5 |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Change From Baseline in LPP for Group D-527.51 Rollover | Baseline (N= 53 (LD), 12 (MD), 29(HD)) | 48.50 cm H2O | Standard Deviation 14.47 |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Change (N= 39 (LD), 9 (MD),22 (HD)) | -25.5 cm H2O | Standard Deviation 15.18 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Actual (N= 39 (LD), 9 (MD),22 (HD)) | 49.50 cm H2O | Standard Deviation 8.3 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Change From Baseline in LPP for Group D-527.51 Rollover | Baseline (N= 53 (LD), 12 (MD), 29(HD)) | 48.5 cm H2O | Standard Deviation 11.19 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Change (N= 39 (LD), 9 (MD),22 (HD)) | -2 cm H2O | Standard Deviation 13.68 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Change From Baseline in LPP for Group D-527.51 Rollover | Baseline (N= 53 (LD), 12 (MD), 29(HD)) | 55.50 cm H2O | Standard Deviation 24.52 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Change (N= 39 (LD), 9 (MD),22 (HD)) | -1.25 cm H2O | Standard Deviation 24.97 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Actual (N= 39 (LD), 9 (MD),22 (HD)) | 64.75 cm H2O | Standard Deviation 27.2 |
Secondary
CL/F,ss,W,Norm
Weight-normalized CL/F,ss (apparent clearance of the analyte in the plasma at steady state after extravascular multiple dose administration), CL/F,ss,W,norm. Weight-normalized CL/F,ss was calculated by dividing the respective quantities by body weight in kg. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | CL/F,ss,W,Norm | 0.0383 L/h/kg | Geometric Coefficient of Variation 91.1 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | CL/F,ss,W,Norm | 0.0397 L/h/kg | Geometric Coefficient of Variation 82.9 |
| Tamsulosin - High Dose Level (Group D-Denovo) | CL/F,ss,W,Norm | 0.0361 L/h/kg | Geometric Coefficient of Variation 59.1 |
Secondary
Cmax,1
Maximum measured concentration of the analyte in plasma following the first dose, Cmax,1. This Outcome Measure was only pre-specified for PK Study- single dose group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h and 8h after the drug administration.
Population: Pharmacokinetics single dose set (PK-SD): This set includes subjects who were randomized, successfully took and retained the first dose of study medication and provided blood samples for PK at Visit 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Cmax,1 | 1.67 ng/mL | Geometric Coefficient of Variation 68.8 |
Secondary
Cmax, 1 ,DW ,Norm
Dose- and weight-normalized Cmax,1 (Cmax,1,DW,norm). Weight normalization of Cmax,1 was performed by dividing the respective quantities by the reciprocal of body weight in kg. This Outcome Measure was only pre-specified for PK Study- single dose group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h and 8h after the drug administration.
Population: Pharmacokinetics single dose set (PK-SD)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Cmax, 1 ,DW ,Norm | 1120 ng/mL/mg*kg | Geometric Coefficient of Variation 67.2 |
Secondary
Cmax,ss
Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ, Cmax,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Cmax,ss | 2.79 ng/mL | Geometric Coefficient of Variation 59.5 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Cmax,ss | 5.02 ng/mL | Geometric Coefficient of Variation 94.8 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Cmax,ss | 14.10 ng/mL | Geometric Coefficient of Variation 50.3 |
Comparison: Dose proportionality for Cmax,ss was explored based on the regression model.95% CI: [0.6499, 1.3579]
Secondary
Cmax,ss, DW, Norm
Dose- and weight-normalized for Cmax,ss, Cmax,ss, DW, norm. Weight normalization of Cmax,ss was performed by dividing the respective quantities by the reciprocal of body weight in kg. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Cmax,ss, DW, Norm | 2040 ng/mL/mg*kg | Geometric Coefficient of Variation 74.3 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Cmax,ss, DW, Norm | 1850 ng/mL/mg*kg | Geometric Coefficient of Variation 85.7 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Cmax,ss, DW, Norm | 2240 ng/mL/mg*kg | Geometric Coefficient of Variation 47.6 |
Secondary
Cmin,ss
Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ, Cmin,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Cmin,ss | 0.747 ng/mL | Geometric Coefficient of Variation 99.7 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Cmin,ss | 1.52 ng/mL | Geometric Coefficient of Variation 130 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Cmin,ss | 4.01 ng/mL | Geometric Coefficient of Variation 68.5 |
Secondary
Cpre,ss
Pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose, Cpre,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS): This set includes subjects who were randomized successfully took study medication for two weeks at their randomized dose level and provided blood samples for PK at their steady state visit.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Cpre,ss | 0.914 ng/mL | Geometric Coefficient of Variation 159 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Cpre,ss | 1.83 ng/mL | Geometric Coefficient of Variation 131 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Cpre,ss | 4.03 ng/mL | Geometric Coefficient of Variation 70.6 |
Secondary
Early Responders Who Maintained Their LPP Below 40 cm H2O During the Study for Group D-Denovo and Group D-527.51 Rollover
Early responders who maintained their detrusor leak point pressure (LPP) below 40 cm H2O during the study. Timeframe for Group D-Denovo: Low dose: Week 1, 3 & 4 prior to dose and Week 2, 9 & 26 (optional), 13(additional) & 52 post dose. Medium dose: Week 1, 2 & 4 prior to dose and Week 3, 9(optional), 13(additional), 26 (optional) & 52 post dose. High dose: Week 1, 2 & 3 prior to dose administration and Week 4, 9(optional), 13(additional), 26 (optional) & 52 post dose. Group D-527.51 Rollover: Week 1, 2,3 & 4 prior to dose and Week 9 &26 (optional),13 (additional) & 52 post dose. This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, However this endpoint was not analysed for Group D-527.51 Rollover as very limited data were collected due to early termination of the study & no alternative endpoint was defined in the Group D-527.51 rollover, so only the results for Group D-Denovo is provided.
Time frame: Week 1 to Week 52 (Time frame for all weeks are described study wise in the Description).
Population: Full analysis set (FAS-LPP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Early Responders Who Maintained Their LPP Below 40 cm H2O During the Study for Group D-Denovo and Group D-527.51 Rollover | 17 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Early Responders Who Maintained Their LPP Below 40 cm H2O During the Study for Group D-Denovo and Group D-527.51 Rollover | 5 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Early Responders Who Maintained Their LPP Below 40 cm H2O During the Study for Group D-Denovo and Group D-527.51 Rollover | 3 Participants |
Secondary
LPP Response at Any Time During the Trial for Group D-Denovo and Group D-527.51 Rollover
Response rates of LPP responders (2 LPP values \< 40 cm H2O) at any time during the trial by treatment group. Timeframe for Group D-Denovo: Low dose: Week 1, 3 & 4 prior to dose and Week 2, 9 & 26 (optional), 13(additional) & 52 post dose. Medium dose: Week 1, 2 & 4 prior to dose and Week 3, 9(optional), 13(additional), 26 (optional) & 52 post dose. High dose: Week 1, 2 & 3 prior to dose administration and Week 4, 9(optional), 13(additional), 26 (optional) & 52 post dose. Group D-527.51 Rollover: Week 1, 2, 3 & 4 prior to dose and Week 9 &26 (optional),13 (additional) & 52 post dose. This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, so results of these two groups are provided.
Time frame: Week 1 to Week 52 (described study wise in the Description).
Population: Full analysis set (FAS-LPP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | LPP Response at Any Time During the Trial for Group D-Denovo and Group D-527.51 Rollover | 26 participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | LPP Response at Any Time During the Trial for Group D-Denovo and Group D-527.51 Rollover | 16 participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | LPP Response at Any Time During the Trial for Group D-Denovo and Group D-527.51 Rollover | 16 participants |
| Tamsulosin - Low Dose Level (Group D-527.51 Rollover) | LPP Response at Any Time During the Trial for Group D-Denovo and Group D-527.51 Rollover | 42 participants |
| Tamsulosin - Medium Dose Level (Group D-527.51 Rollover) | LPP Response at Any Time During the Trial for Group D-Denovo and Group D-527.51 Rollover | 8 participants |
| Tamsulosin - High Dose Level (Group D-527.51 Rollover) | LPP Response at Any Time During the Trial for Group D-Denovo and Group D-527.51 Rollover | 12 participants |
Secondary
MRTpo,ss
Mean residence time of the analyte in the body at steady state after oral administration,MRTpo,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | MRTpo,ss | 18.70 hours | Geometric Coefficient of Variation 50.5 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | MRTpo,ss | 17.60 hours | Geometric Coefficient of Variation 35 |
| Tamsulosin - High Dose Level (Group D-Denovo) | MRTpo,ss | 20.90 hours | Geometric Coefficient of Variation 23.6 |
Secondary
Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo
Number of participants with Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse events and Cognitive Testing. Relevant findings or worsening of baseline conditions were reported as adverse events. Subjects who experienced orthostatic hypotension during orthostatic testing were reported as adverse events. This Outcome Measure was only pre-specified for Group D-Denovo, so results of this group is provided.
Time frame: From first drug administration until 28 days after last study drug administration, upto 450 days
Population: Treated Set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | Body temperature increased | 0 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | Blood urine present | 0 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | Orthostatic hypotension | 1 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | Body temperature increased | 0 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | Blood urine present | 0 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | Orthostatic hypotension | 3 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | Blood urine present | 1 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | Orthostatic hypotension | 0 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse Events and Cognitive Testing for Group D-Denovo | Body temperature increased | 1 Participants |
Secondary
Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values,Urinalysis,Occurence of Adverse Events & Cognitive Testing for Group D-527.51 Rollover
Number of participants with Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic testing, Electrocardiogram (ECG), Laboratory Values, Urinalysis, Occurence of Adverse events and Cognitive Testing. Relevant findings or worsening of baseline conditions were reported as adverse events. Below mentioned result are the number of subjects who had the clinical relevant abnormalities for the preferred term 'Hepatic enzyme increased'. This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided.
Time frame: From first drug administration until 28 days after last study drug administration, upto 395 days
Population: Treated Set (TS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values,Urinalysis,Occurence of Adverse Events & Cognitive Testing for Group D-527.51 Rollover | 1 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values,Urinalysis,Occurence of Adverse Events & Cognitive Testing for Group D-527.51 Rollover | 0 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Number of Participants With Clinically Relevant Abnormalities for Physical Examination, Vital Signs/Orthostatic Testing, Electrocardiogram (ECG), Laboratory Values,Urinalysis,Occurence of Adverse Events & Cognitive Testing for Group D-527.51 Rollover | 0 Participants |
Secondary
Percent Change From Baseline in LPP for Group D-527.51 Rollover
Percent change from baseline in actual detrusor leak point pressure (LPP) by treatment group (subjects are classified according to the treatment they were taking at end of treatment) and Week. Baseline assessments were obtained from trial 527.51 for Group D-527.51 Rollover. The results from Week 1 were reported because there were very few subjects who reported data at subsequent visits due to the termination of the trial. This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided.
Time frame: Baseline and Week 1
Population: Full analysis set (FAS-LPP)
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Percent Change From Baseline in LPP for Group D-527.51 Rollover | Baseline (N= 53 (LD), 12 (MD), 29 (HD)) | 48.50 percent change | Standard Deviation 14.47 |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Percent Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Change (N= 39 (LD), 9 (MD), 22 (HD)) | -48.48 percent change | Standard Deviation 18.65 |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Percent Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Actual (N= 39 (LD), 9 (MD), 22 (HD)) | 29.00 percent change | Standard Deviation 8.5 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Percent Change From Baseline in LPP for Group D-527.51 Rollover | Baseline (N= 53 (LD), 12 (MD), 29 (HD)) | 48.50 percent change | Standard Deviation 11.19 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Percent Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Actual (N= 39 (LD), 9 (MD), 22 (HD)) | 49.50 percent change | Standard Deviation 8.3 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Percent Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Change (N= 39 (LD), 9 (MD), 22 (HD)) | -3.88 percent change | Standard Deviation 22.43 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Percent Change From Baseline in LPP for Group D-527.51 Rollover | Baseline (N= 53 (LD), 12 (MD), 29 (HD)) | 55.50 percent change | Standard Deviation 24.52 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Percent Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Change (N= 39 (LD), 9 (MD), 22 (HD)) | -2.71 percent change | Standard Deviation 40.41 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Percent Change From Baseline in LPP for Group D-527.51 Rollover | Week 1 - Actual (N= 39 (LD), 9 (MD), 22 (HD)) | 64.75 percent change | Standard Deviation 27.2 |
Secondary
RA,Cmax
The accumulation ratio was calculated from the patients who were randomised to the low dose group and for whom both parameters at first dose and steady state dose were available. Accumulation ratios of tamsulosin HCl in plasma at steady state after multiple dose administration over a uniform dosing interval τ, expressed as ratio of Cmax at steady state and after single dose. The accumulation ratio RA,Cmax was calculated as: Cmax,ss/Cmax,1. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results from this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | RA,Cmax | 1.58 Ratio | Geometric Coefficient of Variation 65.2 |
Secondary
Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover
Response defined as stabilization or improvement of hydronephrosis measured by renal ultrasound compared to baseline by treatment group (subjects are classified according to the treatment they were taking at Week 52 or end of treatment) at week 52 for Group D-Denovo and (subjects are classified according to the treatment they were taking at the end of treatment) at last value on treatment for Group D-527.51 Rollover. Baseline assessments were obtained from trial 527.51 for Group D-527.51 Rollover. The overall treatment duration was not sufficient to reach any meaningful conclusions regarding improvement or stabilization of hydronephrosis in the Group D-527.51 Rollover. Hydronephrosis response is defined as an improvement or stabilization based upon ultrasound grading at the end of the study. The lower or same grade at end of treatment compared to baseline is considered an improvement or stabilization.
Time frame: Group D-Denovo: Baseline and Week 52. Group D-527.51 Rollover: Baseline, Week 26 and Week 52.
Population: Full analysis set (FAS-RENAL). This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, so results of these two groups are provided.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 26 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 24 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 15 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 14 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 28 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 26 Participants |
| Tamsulosin - Low Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 39 Participants |
| Tamsulosin - Low Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 42 Participants |
| Tamsulosin - Medium Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 8 Participants |
| Tamsulosin - Medium Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 7 Participants |
| Tamsulosin - High Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 17 Participants |
| Tamsulosin - High Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydronephrosis Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 17 Participants |
Secondary
Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover
Response defined as stabilization or improvement of hydroureter measured by renal ultrasound compared to baseline by treatment group (subjects are classified according to the treatment they were taking at Week 52 or end of treatment) at week 52 for Group D-Denovo and (subjects are classified according to the treatment they were taking at the end of treatment) at last value on treatment for Group D-527.51 Rollover. Baseline assessments were obtained from trial 527.51 for Group D-527.51 Rollover. The overall treatment duration was not sufficient to reach any meaningful conclusions regarding improvement or stabilization of hydroureter in the Group D-527.51 Rollover. Hydroureter response is defined as improvement or stabilization based upon the presence or absence of hydroureter at end of treatment compared to baseline. This Outcome Measure was only pre-specified for Group D-Denovo and Group D-527.51 Rollover subjects, so results of these two groups are provided.
Time frame: Group D-Denovo: Baseline and Week 52. Group D-527.51 Rollover: Baseline, Week 26 and Week 52.
Population: Full analysis set (FAS-RENAL): Includes all patients in the Treated set who received one dose of treatment and had one on treatment renal measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 26 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 24 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 15 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 14 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 28 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 29 Participants |
| Tamsulosin - Low Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 43 Participants |
| Tamsulosin - Low Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 43 Participants |
| Tamsulosin - Medium Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 8 Participants |
| Tamsulosin - Medium Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 8 Participants |
| Tamsulosin - High Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Right Kidney | 19 Participants |
| Tamsulosin - High Dose Level (Group D-527.51 Rollover) | Response Defined as Stabilization or Improvement of Hydroureter Measured by Renal Ultrasound Compared to Baseline for Group D-Denovo and Group D-527.51 Rollover | Left Kidney | 17 Participants |
Secondary
t1/2,ss
Terminal half-life of the analyte in plasma at steady state, t1/2,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | t1/2,ss | 11.80 hours | Geometric Coefficient of Variation 48.1 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | t1/2,ss | 10.30 hours | Geometric Coefficient of Variation 40.8 |
| Tamsulosin - High Dose Level (Group D-Denovo) | t1/2,ss | 14.00 hours | Geometric Coefficient of Variation 31.9 |
Secondary
Tmax, 1
Time from dosing to maximum measured concentration of the analyte in plasma after administration of the first dose, tmax, 1. This Outcome Measure was only pre-specified for PK Study- single dose group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h and 8h after the drug administration.
Population: Pharmacokinetics single dose set (PK-SD)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Tmax, 1 | 6 hours |
Secondary
Tmax,ss
Time from last dosing to maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ, tmax,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Tmax,ss | 5.00 hours | Full Range 99.7 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Tmax,ss | 5.92 hours | Full Range 130 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Tmax,ss | 5.01 hours | Full Range 68.5 |
Secondary
Vision Testing for Group D-527.51 Rollover
Number of subjects with a change from baseline in visual acuity by treatment group (subjects are classified according to the treatment they were taking at end of treatment). They were analysed based on the below mentioned category in both the Eyes: 1) No Change 2) Decrease in visual acuity 3) Increase in visual acuity 4) Missing. Missing includes subjects with no baseline exam and subjects with exam scores missing. This Outcome Measure was only pre-specified for Group D-527.51 Rollover subjects, so results of this group is provided.
Time frame: Baseline and Week 52
Population: Treated Set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - No Change | 32 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - Decrease in visual acuity | 5 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - Increase in visual acuity | 12 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - Missing | 5 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - No Change | 31 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - Decrease in visual acuity | 8 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - Increase in visual acuity | 10 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - Missing | 5 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - Increase in visual acuity | 1 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - Increase in visual acuity | 0 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - Missing | 0 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - No Change | 12 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - Decrease in visual acuity | 1 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - No Change | 10 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - Decrease in visual acuity | 2 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - Missing | 0 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - Increase in visual acuity | 6 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - Decrease in visual acuity | 4 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - No Change | 12 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Right Eye - Missing | 7 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - Increase in visual acuity | 7 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - Decrease in visual acuity | 3 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - No Change | 12 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-527.51 Rollover | Left Eye - Missing | 7 Participants |
Secondary
Vision Testing for Group D-Denovo
Number of subjects with a change from baseline in visual acuity by treatment group (subjects are classified according to the treatment they were taking at Week 52 or end of treatment). They were analysed based on the below mentioned category in both the Eyes: 1) No Change 2) Decrease in visual acuity 3) Increase in visual acuity 4) Missing. Missing includes subjects with no baseline exam and subjects with exam scores missing. This Outcome Measure was only pre-specified for Group D-Denovo subjects, so results of this group is provided.
Time frame: Baseline, Week 26 and Week 52.
Population: Treated Set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - Increase in visual acuity | 11 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - Decrease in visual acuity | 7 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - Decrease in visual acuity | 8 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - Decrease in visual acuity | 10 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - Increase in visual acuity | 9 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - No Change | 11 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - Missing | 2 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - Increase in visual acuity | 11 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - Increase in visual acuity | 8 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - No Change | 7 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - Decrease in visual acuity | 6 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - Missing | 2 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - No Change | 11 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - Missing | 1 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - No Change | 11 Participants |
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - Missing | 1 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - Missing | 9 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - No Change | 7 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - Decrease in visual acuity | 1 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - Increase in visual acuity | 4 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - No Change | 6 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - Decrease in visual acuity | 1 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - Increase in visual acuity | 5 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - Missing | 9 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - No Change | 6 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - Decrease in visual acuity | 2 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - Increase in visual acuity | 6 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - Missing | 7 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - No Change | 5 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - Decrease in visual acuity | 3 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - Increase in visual acuity | 7 Participants |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - Missing | 6 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - Increase in visual acuity | 12 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - Missing | 6 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - Missing | 5 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - Missing | 5 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - Missing | 6 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - Increase in visual acuity | 14 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - No Change | 12 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - Increase in visual acuity | 8 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - Increase in visual acuity | 11 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - No Change | 12 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - No Change | 16 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - Decrease in visual acuity | 4 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 52) - Decrease in visual acuity | 6 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 52) - Decrease in visual acuity | 4 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Left Eye (Week 26) - No Change | 19 Participants |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vision Testing for Group D-Denovo | Right Eye (Week 26) - Decrease in visual acuity | 8 Participants |
Secondary
Vz/F,ss,W,Norm
Weight-normalized Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration), Vz/F,ss,W,norm. Weight-normalized VzF,ss was calculated by dividing the respective quantities by body weight in kg. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | Vz/F,ss,W,Norm | 0.65 L/kg | Geometric Coefficient of Variation 83.8 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | Vz/F,ss,W,Norm | 0.591 L/kg | Geometric Coefficient of Variation 103 |
| Tamsulosin - High Dose Level (Group D-Denovo) | Vz/F,ss,W,Norm | 0.729 L/kg | Geometric Coefficient of Variation 96 |
Secondary
λz,ss
Terminal rate constant of the analyte in plasma at steady state, λz,ss. This Outcome Measure was only pre-specified for PK Study- steady state group subjects, so results of this group is provided.
Time frame: -0.25h prior to dose and 2h, 4h, 6h, 8h, 10h, 24h and 33h after the drug administration.
Population: Pharmacokinetics steady state set (PK-SS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tamsulosin - Low Dose Level (Group D-Denovo) | λz,ss | 0.0589 1/hours | Geometric Coefficient of Variation 48.1 |
| Tamsulosin - Medium Dose Level (Group D-Denovo) | λz,ss | 0.0671 1/hours | Geometric Coefficient of Variation 40.8 |
| Tamsulosin - High Dose Level (Group D-Denovo) | λz,ss | 0.0496 1/hours | Geometric Coefficient of Variation 31.9 |