Bioequivalence Study of Nefopam Hydrochloride 30mg Tablets vs Acupan® 30mg Tablets in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to compare the bioavailability of Nefopam Hydrochloride 30mg Tablets (test product) and Acupan® 30mg Tablets (reference product).

Official Title
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A Randomised, Open-label, Single Dose, Crossover Study Investigating the Bioequivalence of Nefopam Hydrochloride 30mg Tablets With Acupan® 30mg Tablets in Healthy Subjects Under Fasting Conditions.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Nefopam Hydrochloride 30mg Tablets
* Drug: Acupan® 30mg Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers aged 18-45 (both inclusive), as determined by medical history, physical examination, laboratory test values, vital signs and 12-lead ECGs at screening. Non-smokers from at least three months before receiving the first dose of study drug and for the duration of the study. Body mass index (BMI) ≥ 18 and ≤ 30 kg/m2. Able to voluntarily provide written informed consent to participate in the study. Must understand the purposes and risks of the study and agree to follow the restrictions and schedule of procedures as defined in the protocol, as confirmed during the informed consent process. Female volunteers of child-bearing potential and less than one year post-menopausal must have a negative serum pregnancy test and be non-lactating. Female volunteers who have been post-menopausal for more than one year and have elevated serum follicle stimulating hormone (FSH) or are treated with hormone replacement therapy (HRT) or female volunteers who have been permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy). Female volunteers of child-bearing potential who are sexually active must use a highly effective method of contraception throughout the study and for 30 days after completion of the study. Acceptable highly effective methods include: established use of oral, injected or implanted hormonal methods of contraception (resulting in a failure rate of less than 1% per year); placement of an intrauterine device or intrauterine system; true abstinence where this is already established as the volunteer's preferred and usual lifestyle; a male partner who has undergone sterilisation (provided that they are the sole sexual partner and that the vasectomised partner has received medical assessment of the surgical success). Male volunteers must not donate sperm during the study and for 90 days after completion of the study. Must be willing to consent to have data entered into The Over Volunteering Prevention System (TOPS). The volunteer's primary care physician has confirmed within the last 12 months that there is nothing in their medical history that would preclude their enrolment into a clinical study. Exclusion Criteria: Volunteers with history or presence of significant cardiovascular disease, pulmonary, hepatic, gallbladder or biliary tract, urogenital (including benign prostatic hypertrophy), haematological, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or current infection. Volunteers with, or at risk of, urinary retention. Laboratory values at screening which are deemed to be clinically significant, unless agreed in advance by the Sponsor's Medical Representative and Principal Investigator. Female volunteers who are pregnant or lactating. Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C. Current or history of drug or alcohol abuse or a positive drugs of abuse or alcohol test at screening or check-in. Participation in a clinical drug study during the 90 days preceding the initial dose in this study. Any clinically significant illness within 30 days prior to study drug administration. Donation of blood or blood products within 90 days prior to study drug administration, or at any time during the study, except as required by this protocol. Volunteers who have a history or presence of any significant drug allergy, including a history of hypersensitivity to nefopam hydrochloride, any related drugs, or any of the excipients contained in the formulations. Use of any prescription or over-the-counter medication (including vitamins, herbal and mineral supplements) within 14 days prior to study drug administration until the end of the study, with the exception of Investigator approved contraceptives and HRT and paracetamol. Volunteers with inadequate venous access to allow collection of blood samples as required by this protocol. Strenuous exercise, as judged by the Investigator, within 72 hours prior to screening, within 72 hours prior to study drug administration and for the duration of the study until after the post-study medical. Weekly alcohol intake exceeding the equivalent of 14 units per week for females or 21 units per week for males. Consumption of alcoholic beverages within 48 hours prior to study drug administration and during study confinement. Consumption of caffeine or xanthine-containing products within 24 hours prior to study drug administration and during study confinement. Volunteers with a history of convulsive disorders. Volunteers who are taking monoamine oxidase inhibitors, or who have taken monoamine oxidase inhibitors within 14 days prior to study drug administration. Volunteers who are taking tricyclic anti-depressants. Consumption of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade or other products containing grapefruit or Seville oranges within 7 days prior to study drug administration, during study confinement and during the wash-out periods. Volunteers who, in the opinion of the Investigator, are unsuitable for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment 1<br>One tablet of test product (Nefopam Hydrochloride 30mg Tablets) containing 30mg nefopam hydrochloride. | Drug: Nefopam Hydrochloride 30mg Tablets<br> <br> |
| Active Comparator: Treatment 2<br>One tablet of reference product (Acupan® 30mg Tablets) containing 30mg nefopam hydrochloride. | Drug: Acupan® 30mg Tablets<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measurable plasma concentration (Cmax) | Cmax and AUC0-t will be used to calculate bioequivalence of the test product (Treatment 1) vs reference product (Treatment 2). | 0 to 48 hours post-dose | 
| Area under the plasma concentration versus time curve from drug administration to last observed concentration at time t (AUC0-t) | Cmax and AUC0-t will be used to calculate bioequivalence of the test product (Treatment 1) vs reference product (Treatment 2). | 0 to 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, including laboratory parameters. | The safety of volunteers will be monitored by recording adverse events, including laboratory parameters. | 18 days | 
| Time of maximum measured plasma concentration (Tmax) | The pharmacokinetic parameter Tmax will be measured for test and reference products. | 0 to 48 hours post-dose | 
| Elimination rate constant (Kel) | The pharmacokinetic parameter Kel will be measured for test and reference products. | 0 to 48 hours post-dose | 
| Elimination or terminal half-life (t1/2) | The pharmacokinetic parameter t1/2 will be measured for test and reference products. | 0 to 48 hours post-dose | 
| Area under the plasma concentration versus time curve from time zero extrapolated to infinity (AUC0-∞) | The pharmacokinetic parameter AUC0-∞ will be measured for test and reference products. | 0 to 48 hours post-dose |