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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01727791
First received: November 12, 2012
Last updated: April 11, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Healthy Lactating Women
Drug: pregabalin (Lyrica)
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Official Title: A Multiple Dose Pharmacokinetic Open-label Study Of Pregabalin (Lyrica Registered) In Healthy Lactating Women

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 10
Study Start Date: December 2012
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: open label 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.

Detailed Description:
Post approval commitment for the FDA
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01727791

Locations
Belgium
Pfizer Clinical Research Unit
Brussels, Belgium, B-1070
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01727791     History of Changes
Other Study ID Numbers: A0081181  2012-003197-57 
Study First Received: November 12, 2012
Results First Received: April 11, 2016
Last Updated: April 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
pharmacokinetic
pregabalin
lactation

Additional relevant MeSH terms:
Pregabalin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on July 24, 2016