Summary Basis of Decision for Trosec ™
Review decision
The Summary Basis of Decision explains why the product was approved for sale in Canada. The document includes regulatory, safety, effectiveness and quality (in terms of chemistry and manufacturing) considerations.
Product type:
TrosecTM
Trospium chloride, 20 mg, Coated tablet, Oral
Oryx Pharmaceuticals Inc.
Submission control no: 095373
Date issued: 2006-07-31
Health Products and Food Branch
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Health Canada
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Health Products and Food Branch
Également disponible en français sous le titre : Sommaire des motifs de décision (SMD), PrTROSECMD, chlorure de trospium, 20 mg, comprimés enrobés, Oryx Pharmaceuticals Inc., N° de contrôle de la présentation 095373
Foreword
Health Canada's Summary Basis of Decision (SBD) documents outline the scientific and regulatory considerations that factor into Health Canada regulatory decisions related to drugs and medical devices. SBDs are written in technical language for stakeholders interested in product-specific Health Canada decisions, and are a direct reflection of observations detailed within the evaluation reports. As such, SBDs are intended to complement and not duplicate information provided within the Product Monograph.
Readers are encouraged to consult the 'Reader's Guide to the Summary Basis of Decision - Drugs' to assist with interpretation of terms and acronyms referred to herein. In addition, a brief overview of the drug submission review process is provided in the Fact Sheet entitled 'How Drugs are Reviewed in Canada'. This Fact Sheet describes the factors considered by Health Canada during the review and authorization process of a drug submission. Readers should also consult the 'Summary Basis of Decision Initiative - Frequently Asked Questions' document.
The SBD reflects the information available to Health Canada regulators at the time a decision has been rendered. Subsequent submissions reviewed for additional uses will not be captured under Phase I of the SBD implementation strategy. For up-to-date information on a particular product, readers should refer to the most recent Product Monograph for a product. Health Canada provides information related to post-market warnings or advisories as a result of adverse events (AE).
For further information on a particular product, readers may also access websites of other regulatory jurisdictions. The information received in support of a Canadian drug submission may not be identical to that received by other jurisdictions.
Other Policies and Guidance
Readers should consult the Health Canada website for other drug policies and guidance documents. In particular, readers may wish to refer to the 'Management of Drug Submissions Guidance'.
1 Product and submission information
Brand name:
Manufacturer/sponsor:
Medicinal ingredient:
International non-proprietary Name:
Strength:
Dosage form:
Route of administration:
Drug identification number(DIN):
- 02275066
Therapeutic Classification:
Non-medicinal ingredients:
Submission type and control no:
Date of Submission:
Date of authorization:
Trosec™ is a registered trademark of Oryx Pharmaceuticals Inc.
2 Notice of decision
On January 10, 2006 , Health Canada issued a Notice of Compliance to Oryx Pharmaceuticals Inc. for the drug product Trosec. Trosec contains the medicinal ingredient trospium chloride which is an antispasmodic, antimuscarinic agent. Trospium chloride antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder.
Trosec is indicated for the treatment of overactive bladder with symptoms of urge or mixed urinary incontinence, urgency, and urinary frequency.
The market authorization was based on data from submitted quality, preclinical, and clinical studies. The clinical studies consisted primarily of two, double-blind, randomized, placebo-controlled, parallel-group Phase III studies involving approximately 1000 subjects. Trospium chloride significantly decreased urinary frequency and urge incontinence episodes when compared with placebo. The data submitted demonstrated that Trosec can be administered safely when used under the conditions stated in the Product Monograph.
Trosec (20 mg, trospium chloride) is presented as coated tablets. The recommended dose is 20 mg twice daily. Dosage modifications are recommended for patients with severe renal impairment, or geriatric patients 75 years or older. Dosing guidelines are available in the Product Monograph.
Trosec is contraindicated for patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma, and in patients who are at risk for these conditions. The drug is also contraindicated in patients who have demonstrated hypersensitivity to the drug, its ingredients, or any component of the container . Detailed conditions for the use of Trosec are described in the Product Monograph.
Based on the Health Canada review of data on quality, safety, and effectiveness, Health Canada considers that the benefit/risk profile of Trosec is favourable for the treatment of overactive bladder with symptoms of urge or mixed urinary incontinence, urgency, and urinary frequency.
3 Scientific and Regulatory Basis for Decision
3.1 Quality Basis for Decision
3.1.1 Drug Substance (medicinal ingredient)
Manufacturing Process and Process Controls
Materials used in the manufacture of the drug substance, trospium chloride, are considered to be suitable and/or meet standards appropriate for their intended use. The manufacturing process is considered to be adequately controlled within justified limits.
Characterization
Trospium chloride is highly soluble in water and has no known polymorphic forms. The structure of trospium chloride is considered to be adequately elucidated. The representative spectra have been provided.
The impurity profiles are considered to be acceptable. The proposed limits for impurities were considered to be adequately qualified (e.g. within recommended ICH limits and/or limits specified in the European Pharamcopoeia monograph). No impurities were detected at levels above the ICH identification /qualification thresholds.
Control of Drug Substance
Copies of the analytical methods and, where appropriate, validation reports were considered satisfactory for all analytical procedures used for release and stability testing of trospium chloride.
The specifications are considered acceptable for the drug substance. Batch analysis results were reviewed and were within the proposed acceptance criteria.
The proposed packaging components are considered acceptable.
Stability
Stability study results based on accelerated and long-term testing show that trospium chloride is a stable compound when packaged as proposed over the proposed re-test period.
3.1.2 Drug Product
Description and Composition
Trosec tablets are brownish yellow, biconvex, glossy coated tablets, imprinted with a 'T'. Each tablet contains 20 mg of trospium chloride and the following inactive ingredients: sucrose, wheat starch, microcrystalline cellulose, talc, lactose monohydrate, calcium carbonate, titanium dioxide, stearic acid, croscarmellose sodium, povidone, polyethylene glycol 8000, colloidal silicon dioxide, ferric oxide, carboxymethylcellulose sodium, white wax and carnauba wax.
The coated tablets are packaged in a polyvinyl chloride (PVC) blister pack with coated aluminium foil (10 tablets per package).
Pharmaceutical Development
Changes to the manufacturing process and formulation throughout the development are considered acceptable upon review.
Manufacturing Process and Process Controls
The method of manufacturing is considered acceptable and the process is considered adequately controlled within justified limits. The tablet granules are manufactured by a wet granulation method and are compressed into tablets and coated with a sucrose solution to mask the bitter taste and to improve appearance and stability. The manufacturing process for commercial production is well-controlled and yields tablets that meet all relevant specifications.
Control of Drug Product
Trosec tablets are tested to verify that their identity, purity, appearance, content uniformity, dissolution, and levels of degradation products and microbial impurities are within acceptance criteria. The test specifications are considered acceptable to control the drug product, and the impurity limits were set according to ICH recommendations.
Copies of the analytical methods and, where appropriate, validation reports were considered satisfactory for all analytical procedures used for release and stability testing of Trosec.
Batch analysis results were all within the proposed acceptance criteria. Certificates of Analysis have been provided for batches used in clinical studies. The proposed limits for degradation products were considered satisfactorily qualified (e.g., within recommended ICH limits).
Stability
Based upon the long-term and accelerated stability study data submitted, the proposed 60-month shelf-life is considered acceptable when Trosec tablets are packaged in the approved container/closure system and are stored at 15-30°C. Sixty months of stability data for three lots stored under ICH long-term and intermediate conditions, as well as data from six months under ICH accelerated conditions, were within specifications at all times and no trends were noted.
3.1.3 Facilities and Equipment
The design, operations and controls of the facility and equipment that are involved in the production are considered suitable for the products manufactured at the site. All manufacturing sites are listed as being GMP compliant for their listed activities on the Health Canada database.
3.1.4 Adventitious Agents Safety Evaluation
A letter of attestation has been provided which states that the manufacture of Trospium chloride tablets is in compliance with EMEA regulations regarding TSE. Lactose used in the formulation is of animal origin. The lactose supplier has also provided a letter declaring the BSE/TSE safety of all pharmaceutical grades of lactose used in Trosec tablets.
3.1.5 Summary and Conclusion
This New Drug Submission is considered to meet the requirements of Division C.08.002 of the Food and Drug Regulations insofar as the Quality (Chemistry and Manufacturing) information is concerned. The Chemistry and Manufacturing information submitted for Trosec has demonstrated that the drug substance and drug product can be consistently manufactured to meet the specifications agreed upon. Proper development and validation studies were conducted, and adequate controls are in place for the commercial processes.
3.2 Non-Clinical Basis for Decision
3.2.1 Pharmacodynamics
Pharmacodynamic studies were performed with in vitro cell preparations, isolated organ preparations, and intact animals. Cell and organ preparations were obtained from rat, dog and man; the intact animals were rats.
Trospium chloride, the medicinal ingredient of Trosec, was shown to be a muscarinic receptor antagonist with a significant selectivity for the M3 muscarinic receptor, the primary anticholinergic receptor in the pathogenesis of overactive bladder. Trospium chloride showed a stronger affinity for muscarinic receptors of the urinary bladder (1.47 x 10-9M), compared with affinities of 1.92 x 10-9M, 2.67 x 10-9M, and 3.72 x 10-9M in the cerebral cortex, atrium, and salivary glands, respectively, suggesting the potential for fewer unwanted effects. Other in vitro experiments demonstrated the relaxing activity of trospium chloride on contractions of the bladder muscle. Marked inhibition of cholinergic spasms was also demonstrated in the intact animal.
Trospium chloride was screened for possible central nervous system effects in mice. The compound had no adverse effects on motor coordination and climbing performance in the rotating rod test. Antispasmodically effective doses did not diminish pentetrazole-induced convulsions. Effects on sleeping times in hexobarbitone mice were negative. The absence of these central nervous system effects were also confirmed in rats.
Decreases in salivation and gastrointestinal motility were demonstrated. Mydriatic effects were also noted. Two studies were conducted to specifically evaluate the effect of trospium chloride on the potential risk of QT prolongation. These experiments were performed at concentrations much greater than those expected to occur in humans on therapeutic doses, and did not raise any concerns with respect to risk.
3.2.2 Pharmacokinetics
Absorption
Trospium chloride was slowly and incompletely absorbed and had a half-life of approximately 2.5 to 4 hours after oral administration in rats. Linear kinetics occurred in the concentration range similar to that likely to occur in humans receiving a therapeutic dose. Bio-availability was approximately 10%.
Distribution
Trospium chloride is lipophobic and results showed that the drug was only moderately protein-bound. The drug did not show selective organ uptake or prolonged accumulation in specific tissues. Penetration to the brain was minimal.
Metabolism
A small proportion of t rospium chloride was metabolized by the liver (20%) and this did not involve the cytochrome P450 system. The major metabolite was not pharmacologically active.
Excretion
The major route of excretion was renal elimination involving active secretion as well as filtration.
3.2.3 Toxicology
Single-Dose Toxicity
High single doses of trospium chloride were studied in only two rodent species. Rats and mice exhibited clinical signs of hyperactivity, tremor, spasms, tonoclonic convulsions, impaired coordination, postural abnormalities, diminished elicitation of reflexes, reduction in grip strength and tone of the extremities, changes in the colour of the skin and mucous membranes, piloerection, and low body temperatures. After oral administration of high single doses, the calculated lethal dose that killed 50% of the tested animals was approximately 800 times the equivalent therapeutic dose in humans, indicating a satisfactory therapeutic index.
Repeat-Dose Toxicity
Studies were performed over a satisfactory period in two separate species. Both species were able to tolerate high doses (compared with the projected doses in humans) with relatively few adverse effects.
Genotoxicity
Trospium chloride showed no sign of genotoxic/mutagenic potential in the standard tests performed.
Carcinogenicity
Long-term bioassays were carried out in mice and rats. In mice, the findings revealed an increased incidence of lung adenomas in males and females when compared to control group one. In response to these findings, the lungs of the second control group were also examined histologically. The mice re-analysis gave no conclusive evidence of a causal relation to treatment. Similar testing was done in rats. In rats, trospium chloride did not increase the overall tumour incidence and did not induce tumours of types not normally seen. The re-analysis in mice suggests that incidences of proliferative lung lesions were most likely due to chance and not an effect of trospium chloride. There were no further findings indicating that trospium chloride could increase the tumor ratio in any organ.
Reproductive and Development Toxicity
With the exception of the teratogenicity studies, most of the reproductive and development toxicity studies were performed in rodents. On this limited range of species, no evidence of reproductive and development toxicity studies was observed.
3.2.4 Summary and Conclusion
The non-clinical pharmacology and toxicology program for trospium chloride demonstrated that the compound is relatively safe for humans. Animal studies did not raise any significant issues with respect to mutagenicity, carcinogenicity, or reproductive and developmental toxicity. The one possible concern is the possible increase in adenomas in the mouse lung. This observation was an isolated finding and re-analysis tended to discount it. In the absence of corroborative evidence elsewhere, this finding can be discounted.
3.3 Clinical basis for decision
3.3.1 Pharmacodynamics
Trospium chloride demonstrates high affinity for muscarinic receptors, with equipotent binding to M2 and M3 muscarinic receptor subtypes located in the smooth muscle of the bladder. Placebo-controlled studies employing urodynamic variables were conducted in patients with conditions characterized by involuntary detrusor contractions. The results demonstrated that trospium chloride increased maximum cystometric bladder capacity and volume at the first detrusor contraction. Urinary frequency and number of incontinence episodes were decreased.
3.3.2 Pharmacokinetics
Absorption
Trospium chloride was slowly absorbed with maximum plasma concentrations approximately 5 hours following oral dosing. In fasting healthy male subjects, approximately 14% of the single oral doses of 20, 40, or 60 mg trospium chloride was absorbed. Dose proportionality was maintained over the range of therapeutic dosing.
Food had a significant impact on drug absorption. A high fat meal reduced drug absorption resulting in drug exposure values (AUC and Cmax) 70%-80% lower than that obtained with fasting subjects. It is therefore recommended that Trosec be administered to patients on an empty stomach in order to achieve greater drug exposure.
Distribution
Trospium chloride appears to be distributed mostly extracellularly and is less than 80% protein-bound. It is not expected to interfere with the binding of other drugs. The mean absolute bioavailability was approximately 10% over the dose range of 20 to 60 mg trospium chloride. The unabsorbed drug was excreted in the faeces.
Metabolism
Metabolism of trospium chloride occurred to a limited extent. Approximately 80% of the drug in the urine was unchanged drug; approximately 10% was the metabolite azoniaspironortropanol, and less than 10% were two unidentified metabolites. The activity of the metabolites is unknown. In vitro investigations suggest that the major metabolic pathway is not associated with the cytochrome P450 iso-enzyme system.
Elimination
Renal elimination was the predominant mode of excretion. Trospium chloride was actively secreted by the kidney, presumably by the base transport system. After administration of oral 14C-trospium chloride, the majority of the dose (85.2%) was recovered in feces and a smaller amount (5.8% of the dose) was recovered in urine; 60% of the radioactivity excreted in urine was unchanged trospium chloride. Subjects with renal failure were studied and delayed elimination was noted.
Special populations
Age - Pharmacology studies were performed in a small number of elderly subjects and the kinetic parameters were compared with the younger healthy volunteers. In clinical trials, the mean age of the elderly subjects did not exceed 70 years, although, there were patients >75 years included in the studies. Age did not, independently, affect trospium pharmacokinetics, however, the population older than 75 years had greater heterogeneity with respect to hepatic and renal function and has been shown to have an increased incidence of anticholinergic side effects. Based upon tolerability, the dose frequency of Trosec may be reduced to 20 mg once daily in patients 75 years of age and older.
Renal impairment - Twelve patients with renal impairment (mean creatinine clearance 15.3 mL/min, range 8.2-31.9) were studied. Parametric analyses showed statistically significant differences between patients with renal impairment and healthy subjects with respect to drug exposure parameters AUC, Cmax , T1/2, and total renal excretion, of trospium chloride and the metabolite azoniaspironortropanol. Results indicate that the dose of 20 mg trospium chloride administered once daily in patients with impaired renal function is expected to result in similar maximum plasma concentrations as a 20 mg twice daily dose in healthy subjects. Consequently, patients with moderate to severe renal impairment, should be administered Trosec only once a day.
Hepatic impairment - A study was performed in patients with mild and moderate hepatic impairment. The maximum trospium chloride concentration (Cmax) increased 12% and 63% in patients with mild and moderate hepatic impairment, respectively, compared to healthy subjects. The mean area under the plasma concentration-time curve (AUC) was similar. Caution should therefore be used when administering Trosec to patients with moderate and severe hepatic dysfunction.
Drug interactions
Drug interactions associated with metabolism are unlikely because metabolism plays a minor part in the overall elimination of trospium chloride. The sponsor did not investigate drug-drug interactions that might occur on the basis of active renal transport.
3.3.3 Clinical Efficacy
Two pivotal Phase III, placebo-controlled, double-blind, parallel-group, randomized studies were performed in approximately 1000 patients with overactive bladder (OAB) in the United States . The objective was to determine the effects of 20 mg of trospium chloride versus placebo, given twice daily, on OAB associated with urinary frequency, urgency, and urge incontinence over a 12-week treatment period. Both pivotal studies were similar, with the exception that one of the studies had an additional 9-month open-label treatment phase. Additional study results were also obtained from three non-pivotal studies conducted in Europe . The size of the studies, i.e. number of patients involved, was appropriate, and the duration of the studies were acceptable. The randomized population reflected most of the characteristics of the target population except that there was an under-representation of subjects over the age of 75 years.
The co-primary efficacy variables were:
- Change in average number of toilet voids per 24 hours;
- Change in average number of urge incontinence episodes per 24 hours.
The key secondary efficacy variables were:
- Change in average volume voided per toilet void;
- Change in average urgency severity associated with toilet voids.
Overall, the results of the pivotal studies were consistent and showed statistical significance for the key primary and secondary efficacy variables analyzed.
Trospium chloride demonstrated statistically significant (p≤0.05) improvement (i.e., decrease) for the primary efficacy variables of change in average number of toilet voids per 24 hours (at Weeks 1, 4, and 12) and change in average number of urge incontinence episodes per 24 hours (at Weeks 4 and 12) when compared with the placebo group. Although the magnitude of improvement increased from Week 1 to Weeks 4 and 12, the absolute improvement in symptomatology over placebo was relatively small. It should be noted that the placebo effect was significant and accounted for up to 50% of the improvement. The placebo response was associated with a significant reduction in incontinence episodes. The treatment drug added an extra 20% reduction.
Trospium chloride demonstrated statistically significant improvement for the key secondary efficacy variables of change in average volume voided and change in average urgency severity at Weeks 1, 4, and 12 when compared with placebo. Specifically, trospium chloride showed a statistically significant increase in average volume voided and a significant decrease in average urgency severity per 24 hours.
Other secondary endpoints included onset of action during Week 1 for effect on toilet void frequency and urge incontinence episodes per 24 hours. A treatment effect was first observed for reduction in toilet voids at Day 3 and reached statistical significance for both toilet void frequency and urge incontinence episode reductions by Day 7.
The pivotal studies together with the European studies consistently showed an improvement in incontinence episodes and urinary frequency over placebo. As well, urodynamic measurement data were also provided as physiologic evidence supporting the patient urinary diary data in demonstrating the efficacy of trospium chloride. Data showed significant increases in the trospium chloride group for the key urodynamic variables of maximum cystometric bladder capacity, volume at first unstable contraction, or both.
Study results show that the onset of effect for trospium chloride is expected to provide some clinical benefit by significantly decreasing the number of toilet voids, decreasing the number of urge incontinence episodes, and decreasing the number of total micturitions per 24 hours within the first week of treatment.
3.3.4 Clinical Safety
The safety of Trosec was evaluated in the Phase II and Phase III controlled clinical trials. In the controlled studies, 1673 patients were treated with Trosec: 1510 patients with overactive bladder/urge syndrome (detrusor instability) and 163 patients with detrusor hyperreflexia. When uncontrolled off-label and clinical pharmacological studies are taken into account, 2366 patients were exposed to trospium chloride.
Adverse effects were as expected of an anticholinergic drug. The two most common adverse events reported by patients receiving Trosec 20 mg bid were dry mouth and constipation. In the Phase III studies combined, the incidence of dry mouth in the Trosec arm and the placebo arm were 20.1% and 5.8%, respectively. Constipation was 9.6% in the Trosec arm compared to 4.6% in the placebo arm. The incidence of these anti-cholinergic adverse effects were greater in patients >75 years of age. The potential risk of constipation and subacute obstruction is a concern in this age group, therefore a dose reduction was recommended for patients >75 years of age. Other adverse events that occurred ≥1.0% in the Trosec arm were headache (4.2%), fatigue (1.9%), upper abdominal pain (1.5%), aggravated constipation (1.4%), dyspepsia (1.2%), flatulence (1.2%), urinary retention (1.2%), and dry eyes (1.2%).
With respect to uncommon but serious adverse reactions, constipation and the risk of sub-acute obstruction appear to be the most concerning. One death occurred during an uncontrolled clinical trial due to bowel obstruction and this was considered possibly related to trial medication. In the Phase III studies, there was a slight increase of serious adverse effects in the Trosec arm; however, constipation was the only one remotely connected to medication. Adverse effects appeared to be the result of the anticholinergic effects of the drug and no unexpected events appeared.
Patients with moderate renal impairment (creatinine clearance 15-30 mL/min) were investigated and treatment with Trosec resulted in a significant accumulation of the drug. A dose reduction was therefore recommended. Patients with severe renal failure (creatinine clearance <15 mL/min) were not investigated.
Patients with hepatic dysfunction were investigated and significant drug retention was found in patients with moderate to severe hepatic dysfunction (Child Pugh classes B and C). Caution should be advised when administering Trosec to patients with moderate-severe hepatic dysfunction.
Extensive testing of Trosec was performed to ascertain the potential for causing cardiac arrhythmias and Torsades du Point (including ECGs on a subject with a drug concentration up to the maximum expected in patients with renal failure). Testing was within ICH guideline standards and doses up to 5 times the maximum recommended therapeutic dose were used. Trospium chloride induced a small increase in heart rate, however, it did not appear to have an effect on cardiac repolarization as measured by QTcF intervals or other significant ECG parameters when compared to placebo. No potential for QT prolongation was found, although testing was not performed on subjects with possible "provoking" conditions such as hypokalemia and congestive cardiac failure.
3.4 Benefit/Risk Assessment and Recommendation
3.4.1 Benefit/Risk Assessment
Overactive bladder (OAB) is a condition in which the smooth muscle of the bladder shows greater activity than normal and causes distressing but not life threatening symptoms such as urinary frequency, urgency of micturition as well as incontinence. Trosec contains the medicinal ingredient trospium chloride which is a muscarinic receptor antagonist that reduces the tonus of smooth muscle in the bladder. In the clinical studies, trospium chloride significantly decreased urinary frequency and urge incontinence episodes when compared with placebo. The data from these studies support the conclusion that trospium chloride 20 mg bid is an effective and generally safe treatment option in patients with OAB with predominant urge incontinence.
The common side effects of Trosec are dry mouth and constipation. Similar drugs with the same pharmacological function cause prolonged QT intervals and thus have a potential to cause cardiac arrhythmias and Torsades de Point. Trosec has been investigated for this potential adverse effect according to the standard of the provisional ICH Guideline E14; no evidence of significant prolongation of the QT interval compared to placebo was detected in normal volunteers (25-45 years) at doses ranging from 20 mg to 100 mg bid.
The target therapeutic population for treatment with Trosec includes elderly subjects with multiple co-morbidities. Individualized instructions and continuous supervision of therapy in all subjects and particularly in the elderly are recommended.
3.4.2 Recommendation
Based on the Health Canada review of data on quality, safety and efficacy, Health Canada considers that the benefit/risk profile of Trosec is favourable in the treatment of overactive bladder with symptoms of urge or mixed urinary incontinence, urgency, and urinary frequency. The New Drug Submission complies with the requirements of sections C.08.002 and C.08.005.1 and therefore Health Canada has granted the Notice of Compliance pursuant to section C.08.004 of the Food and Drug Regulations.
4 Submission Milestones
Submission Milestones: TrosecTM
| Submission Milestone | Date |
|---|---|
| Submission filed | 2004-11-22 |
| Screening 1 | |
| Screening Deficiency Notice issued | 2005-01-07 |
| Response filed | 2005-01-31 |
| Screening Acceptance Letter issued | 2005-03-17 |
| Review 1 | |
| Quality Evaluation complete | 2005-12-16 |
| Clinical Evaluation complete | 2006-01-09 |
| Labelling Review complete | 2006-01-06 |
| NOC issued by Director General | 2006-01-10 |
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| TROSEC | 02275066 | SUNOVION PHARMACEUTICALS CANADA INC | TROSPIUM CHLORIDE 20 MG |