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Trial record 1 of 1 for:    NCT01727791
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A Study Of Pregabalin (Lyrica) Drug Levels In Urine, Plasma And Breast Milk Of Healthy Lactating Women

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ClinicalTrials.gov Identifier: NCT01727791
Recruitment Status : Completed
First Posted : November 16, 2012
Results First Posted : May 18, 2016
Last Update Posted : May 18, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE November 12, 2012
First Posted Date  ICMJE November 16, 2012
Results First Submitted Date  ICMJE April 11, 2016
Results First Posted Date  ICMJE May 18, 2016
Last Update Posted Date May 18, 2016
Study Start Date  ICMJE December 2012
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) [ Time Frame: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3 ]
    Area under the plasma concentration-time profile from time 0 to tau (AUCtau), where tau was the dosing interval of 12 hours.
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12, 18, 24 hours post-dose on Day 3 ]
    Cmax was the peak concentration in plasma post Day 3 dose.
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12, 18, 24 hours post-dose on Day 3 ]
    Tmax was the time to peak concentration in plasma post Day 3 dose.
  • Plasma Half-Life (t1/2) [ Time Frame: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12, 18, 24 hours post-dose on Day 3 ]
    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.
  • Average Plasma Concentration During the Dosing Interval (Cav) [ Time Frame: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3 ]
    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.
  • Minimum Observed Plasma Trough Concentration (Cmin) [ Time Frame: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12, 18, 24 hours post-dose on Day 3 ]
    Cmin was the minimum observed plasma concentration of a drug after post Day 3 dose.
  • Apparent Oral Clearance (CL/F) [ Time Frame: Pre-dose on Day 3; 0.5, 1, 2, 3, 4, 6, 10, 12 hours post-dose on Day 3 ]
    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.
  • Area Under the Curve From Time Zero to End of Dosing Interval for Breast Milk (AUCtau [Breast Milk]) [ Time Frame: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 ]
    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.
  • Maximum Observed Concentration in Breast Milk (Cmax [Breast Milk]) [ Time Frame: 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 ]
    Cmax (breast milk) was the maximum observed concentration in breast milk post Day 3 dose.
  • Time to Reach Maximum Observed Breast Milk Concentration (Tmax [Breast Milk]) [ Time Frame: 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 ]
    Tmax (breast milk) was time of the maximum observed breast milk concentration Day 3 post-dose.
  • Terminal Half-Life for Breast Milk (t1/2 [Breast Milk]) [ Time Frame: 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 ]
    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.
  • Average Breast Milk Concentration During the Dosing Interval (Cav) [ Time Frame: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 ]
    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.
  • Amount Excreted in Breast Milk Over the Dosing Interval Tau (Aetaubm) [ Time Frame: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 ]
    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.
  • Percentage of Dose Excreted in Breast Milk During the Dosing Interval Tau (Aetaubm Percent) [ Time Frame: 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) 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.
  • Breast Milk Clearance (CLbm) [ Time Frame: 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 ]
    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.
  • Amount Recovered in Urine During the Dosing Interval Tau (Aetauurine) [ Time Frame: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 ]
    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.
  • Percent of Dose Recovered in Urine During the Dosing Interval Tau (Aetauurine Percent) [ Time Frame: 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) 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.
  • Renal Clearance (CLr) [ Time Frame: 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 ]
    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.
  • Daily Amount of Pregabalin Excreted in Breast Milk (Ae24bm) [ Time Frame: Pre-dose on Day 3; 0 to 2, 2 to 4, 4 to 8, 8 to 12 hours post-dose on Day 3 ]
    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.
  • Milk to Plasma Ratio for AUCtau (MPAUCtau) [ Time Frame: 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 ]
    MPAUCtau was the ratio of AUCtau (breast milk) to AUCtau (plasma), where tau was the dosing interval of 12 hours.
  • Milk to Plasma Ratio for Maximum Observed Concentration (MPCmax) [ Time Frame: 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 ]
    Milk to plasma ratio for maximum observed concentration (MPCmax) was calculated as the ratio of Cmax (breast milk) to Cmax (plasma).
  • Body Weight Normalized Infant Dose (BWNID) [ Time Frame: 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 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.
  • Body Weight Normalized Maternal Dose (BWNMD) [ Time Frame: Pre-dose to 24 hours post-dose on Day 3 ]
    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.
  • Infant Dose Expressed as Percentage of Body Weight Normalized Maternal Dose (BWNIDPCM) [ Time Frame: Pre-dose to 24 hours post-dose on Day 3 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 15, 2012)
  • Area Under the Curve from Time Zero to end of dosing interval (AUCtau) (plasma and breast milk) [ Time Frame: 0.5, 1, 2, 3, 4, 6, 10, and 12 hours post dose on Day 3 ]
  • Maximum Observed Plasma Concentration (Cmax) (plasma and breast milk) [ Time Frame: 0.5, 1, 2, 3, 4, 6, 10, and 12 hours post dose on Day 3 ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) (plasma and breast milk) [ Time Frame: 0.5, 1, 2, 3, 4, 6, 10, and 12 hours post dose on Day 3 ]
  • Plasma Decay Half-Life (t1/2) (plasma and breast milk) [ Time Frame: 2, 3, 4, 6, 10, and 12 hours post dose on Day 3 ]
  • Caverage (plasma only) [ Time Frame: 0.5, 1, 2, 3, 4, 6, 10, and 12 hours post dose on Day 3 ]
  • Minimum Observed Plasma Trough Concentration (Cmin) (plasma only) [ Time Frame: 0.5, 1, 2, 3, 4, 6, 10, and 12 hours post dose on Day 3 ]
  • Apparent Oral Clearance (CL/F) (plasma only) [ Time Frame: 0.5, 1, 2, 3, 4, 6, 10, and 12 hours post dose on Day 3 ]
  • Ae.tau.bm [Amount excreted in breast milk over the dosing interval tau (12 hours)] [ Time Frame: 0 to 2 hours, 2 to 4 hours, 4 to 8 hours, 8 to 12 and 12 to 24 hrs post Day 3 dose ]
  • CL.bm [Breast milk clearance Ae(tau)bm/plasma AUC(tau)] [ Time Frame: Day 3 ]
  • Ae.tau.urine [Amount recovered in urine during the dosing interval, tau (12 hours)] [ Time Frame: Day 3 ]
  • Clr [Renal clearance; Urine Ae(tau)/ Plasma AUC(tau)] [ Time Frame: Day 3 ]
Change History Complete list of historical versions of study NCT01727791 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: April 11, 2016)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 28 days after last dose of study drug ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
  • Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to 28 days after last dose of study drug ]
    The following parameters were analyzed for laboratory abnormalities: hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], platelets, white blood cell count, lymphocytes, total neutrophils, basophils, eosinophils, monocytes); liver function (bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, albumin); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose); urinalysis (urine pH, glucose, ketones, protein, urine blood/hemoglobin, nitrite).
  • Number of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: Baseline up to 28 days after last dose of study drug ]
    The following parameters were analyzed for examination of vital signs: electrocardiogram (ECG), systolic and diastolic blood pressure, temperature, pulse rate, respiratory rate, radial pulse and body temperature.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Of Pregabalin (Lyrica) Drug Levels In Urine, Plasma And Breast Milk Of Healthy Lactating Women
Official Title  ICMJE A Multiple Dose Pharmacokinetic Open-label Study Of Pregabalin (Lyrica Registered) In Healthy Lactating Women
Brief Summary 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 Post approval commitment for the FDA
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Masking: None (Open Label)
Condition  ICMJE Healthy Lactating Women
Intervention  ICMJE Drug: pregabalin (Lyrica)
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.
Study Arms  ICMJE Experimental: open label
Intervention: Drug: pregabalin (Lyrica)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 15, 2012)
10
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2013
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01727791
Other Study ID Numbers  ICMJE A0081181
2012-003197-57 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP