A Study Of Pregabalin (Lyrica) Drug Levels In Urine, Plasma And Breast Milk Of Healthy Lactating Women

Study Overview
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Brief Summary
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This is a pharmacokinetic study to determine the safety and tolerability of pregabalin in healthy lactating women. The objectives are to determine whether pregabalin is secreted in breast milk and if so, to characterize pregabalin pharmacokinetics in breast milk. Other objectives are to estimate potential infant exposure to pregabalin if administered to lactating women and to characterize the safety and tolerability of pregabalin in lactating women.

Detailed Description
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Post approval commitment for the FDA

Official Title
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A Multiple Dose Pharmacokinetic Open-label Study Of Pregabalin (Lyrica Registered) In Healthy Lactating Women

Conditions
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Healthy Lactating Women

Intervention / Treatment
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* Drug: pregabalin (Lyrica)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy lactating females between the ages of 18 and 45 years (inclusive) who are actively breast-feeding or expressing breast milk and are at least 12 weeks post partum. Subjects must be willing to temporarily discontinue breast feeding their infants before the Day 1 evening dose through to 42 hours after the last dose Exclusion Criteria: History of significant adverse reaction to pregabalin or gabapentin. Subjects pregnant or unwilling or unable to comply with the Lifestyle guidelines presented in the protocol during the study period and through the follow-up visit. Subjects with evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric (including post natal depression), neurologic or allergic disease (including drug allergies, but excluding untreated asymptomatic, seasonal allergies at time of dosing).

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

Sexes Eligible for Study
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Female

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: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: open label<br> | Drug: pregabalin (Lyrica)<br>* Subjects will receive a single 150 mg dose of pregabalin in the evening of Day 1, a 150 mg dose of pregabalin in the morning and evening of Day 2 and a 150 mg dose in the morning of Day 3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Area under the plasma concentration-time profile from time 0 to tau (AUCtau), where tau was the dosing interval of 12 hours. | Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3 | 
| Maximum Observed Plasma Concentration (Cmax) | Cmax was the peak concentration in plasma post Day 3 dose. | Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12, 18, 24 hours post-dose on Day 3 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Tmax was the time to peak concentration in plasma post Day 3 dose. | Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12, 18, 24 hours post-dose on Day 3 | 
| Plasma Half-Life (t1/2) | Plasma decay half-life (t1/2) was the time for the plasma concentration to decrease by one-half. The t1/2 is based on the terminal elimination phase time points from this timeframe. | Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12, 18, 24 hours post-dose on Day 3 | 
| Average Plasma Concentration During the Dosing Interval (Cav) | Average plasma concentration during the dosing interval (Cav) was calculated by dividing AUCtau (plasma) with tau, where tau was the dosing interval of 12 hours. | Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3 | 
| Minimum Observed Plasma Trough Concentration (Cmin) | Cmin was the minimum observed plasma concentration of a drug after post Day 3 dose. | Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12, 18, 24 hours post-dose on Day 3 | 
| Apparent Oral Clearance (CL/F) | Apparent oral clearance (CL/F) was calculated by dividing dose by the AUCtau, where tau was the dosing interval of 12 hours. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. | Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3 | 
| Area Under the Curve From Time Zero to End of Dosing Interval for Breast Milk (AUCtau [Breast Milk]) | AUCtau (breast milk) was the area under the curve for breast milk, from time 0 to tau (AUCtau), where tau was the dosing interval of 12 hours. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Maximum Observed Concentration in Breast Milk (Cmax [Breast Milk]) | Cmax (breast milk) was the maximum observed concentration in breast milk post Day 3 dose. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 hours post-dose on Day 3 | 
| Time to Reach Maximum Observed Breast Milk Concentration (Tmax [Breast Milk]) | Tmax (breast milk) was time of the maximum observed breast milk concentration Day 3 post-dose. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 hours post-dose on Day 3 | 
| Terminal Half-Life for Breast Milk (t1/2 [Breast Milk]) | The terminal half-life for breast milk (t1/2 [breast milk]) was the time measured for breast milk concentration to decrease by one-half. For the first 5 participants enrolled under protocol amendment dated: 18 Sep 2012, breast milk was collected up to 24 hours after Day 3 dosing over the following time intervals: 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24 hours. Terminal half-life was determined over those points characterizing the elimination phase. For the remaining 5 participants, there were 3 additional collection intervals (24 to 32, 32 to 40, 40 to 48 hours) for characterizing the terminal elimination phase. The t1/2 (breast milk) is based on the terminal elimination phase time points from this timeframe. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 hours post-dose on Day 3 | 
| Average Breast Milk Concentration During the Dosing Interval (Cav) | Average breast milk concentration during the dosing interval (Cav) was calculated by dividing AUCtau (breast milk) with tau, where tau was the dosing interval of 12 hours. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Amount Excreted in Breast Milk Over the Dosing Interval Tau (Aetaubm) | Aetaubm was the amount excreted in breast milk over the dosing interval tau (12 hours). It was calculated as the sum of (breast milk concentration * sample volume) for each collection interval from 0 to 12 hours post-dose, where tau was the dosing interval of 12 hours. Sample volume was based on ratio of volume weight and density. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Percentage of Dose Excreted in Breast Milk During the Dosing Interval Tau (Aetaubm Percent) | Percentage of dose excreted in breast milk during the dosing interval tau (Aetaubm percent) was calculated by using the formula: 100*(Aetaubm [sum of {breast milk concentration * sample volume} for each collection interval from 0 to 12 hours post-dose] divided by dose), where tau was the dosing interval of 12 hours. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Breast Milk Clearance (CLbm) | Breast milk clearance (CLbm) was calculated by dividing Aetaubm (sum of [breast milk concentration * sample volume] for each collection interval from 0 to 12 hours post-dose) by plasma AUCtau, where tau was the dosing interval of 12 hours. | Plasma: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3. Breast milk: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Amount Recovered in Urine During the Dosing Interval Tau (Aetauurine) | Aetauurine was the amount excreted in urine over the dosing interval tau (12 hours). It was calculated as the sum of (urine concentration * sample volume) for each collection interval from 0 to 12 hours post-dose, where tau was the dosing interval of 12 hours. Here, sample volume was based on the ratio of volume weight and density. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Percent of Dose Recovered in Urine During the Dosing Interval Tau (Aetauurine Percent) | Percent of dose recovered in urine during the dosing interval tau (Aetauurine percent) was calculated as 100* (Aetau [sum of {urine concentration * sample volume} for each collection interval from 0 to 12 hours post-dose] divided by the dose), where tau was the dosing interval of 12 hours. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Renal Clearance (CLr) | Renal clearance (CLr) was the volume of plasma from which the drug was completely removed by the kidney in a given amount of time. It was calculated by dividing Aetauurine (sum of [urine concentration * sample volume] for each collection interval from 0 to 12 hours post-dose) with the plasma AUCtau, where tau was the dosing interval of 12 hours. | Plasma: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3. Urine: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8 and 8 to 12 hours post-dose on Day 3 | 
| Daily Amount of Pregabalin Excreted in Breast Milk (Ae24bm) | Ae24bm was the daily amount of pregabalin excreted in breast milk. It was calculated by the formula: 2 * Aetaubm (sum of [breast milk concentration * sample volume] for each collection interval from 0 to 12 hours post-dose), where tau was the dosing interval of 12 hours. | Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Milk to Plasma Ratio for AUCtau (MPAUCtau) | MPAUCtau was the ratio of AUCtau (breast milk) to AUCtau (plasma), where tau was the dosing interval of 12 hours. | Plasma: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3. Breast milk: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Milk to Plasma Ratio for Maximum Observed Concentration (MPCmax) | Milk to plasma ratio for maximum observed concentration (MPCmax) was calculated as the ratio of Cmax (breast milk) to Cmax (plasma). | Plasma: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12, 18, 24 hours post-dose on Day 3. Breast milk: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 32, 32 to 40 and 40 to 48 hours post-dose on Day 3 | 
| Body Weight Normalized Infant Dose (BWNID) | Body weight normalized infant dose (BWNID) of pregabalin was the dose that an infant received from breast-feeding and was calculated from the milk to plasma AUCtau ratio multiplied by the average maternal plasma pregabalin concentration (Cav) multiplied by the standardized milk consumption for an infant (150 milliliter/kilogram/day [mL/kg/day]), where tau was the dosing interval of 12 hours. | Plasma: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3. Breast milk: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 | 
| Body Weight Normalized Maternal Dose (BWNMD) | Body weight normalized maternal dose (BWNMD) was calculated as the maternal dose in microgram per day (mcg/day) divided by maternal weight in kilogram (kg) at screening. | Pre-dose to 24 hours post-dose on Day 3 | 
| Infant Dose Expressed as Percentage of Body Weight Normalized Maternal Dose (BWNIDPCM) | Infant dose expressed as percentage of body weight normalized maternal dose (BWNIDPCM) was the relative infant dose (relative to maternal dose) calculated by the formula: 100 * BWNID (Body Weight Normalized Infant Dose) / Body Weight Normalized Maternal Dose (BWNMD), where tau was the dosing interval of 12 hours. | Pre-dose to 24 hours post-dose on Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetic, pregabalin, lactation