Trial Outcomes & Findings for Pharmacokinetics of Amlodipine Besylate at Delivery and During Lactation (NCT NCT02353806)

Results Overview

The time to peak amlodipine concentration in the maternal serum in the peripartum period was be measured.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

16 participants

Primary outcome timeframe

Maternal blood samples will be obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing

Results posted on

2019-02-06

Participant Flow

Participant milestones

Participant milestones
Measure	Pregnant Women Taking Amlodipine Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Overall Study STARTED	16
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Amlodipine Besylate at Delivery and During Lactation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pregnant Women Taking Amlodipine n=16 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Age, Continuous	33.2 years STANDARD_DEVIATION 5.8 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	NA Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	12 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Maternal blood samples will be obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing

Population: Although 16 women were enrolled in the study, only 11 of the 16 had blood drawn at the time of delivery. This was due to limitations of study personnel availability to attend the deliveries of all study patients

The time to peak amlodipine concentration in the maternal serum in the peripartum period was be measured.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=11 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Area Under the Curve for Amlodipine in the Maternal Serum	53.4 (hr*ng)/mL Standard Deviation 19.8

PRIMARY outcome

Timeframe: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing

Population: Although 16 women were enrolled in the trial, only 11 had their blood drawn at the time of delivery due to limited availability of study personnel.

The time to reach maximal amlodipine concentration in the maternal serum in the peripartum period was measured.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=11 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Time to Maximal Concentration in the Maternal Serum.	7.5 Hours Standard Deviation 1.5

PRIMARY outcome

Timeframe: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing

Population: Although 16 women were enrolled in the trial, only 11 had their blood drawn at the time of delivery due to limited availability of study personnel.

The maximum concentration of amlodipine detected in the maternal serum in the peripartum period was measured.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=11 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Maximal Amlodipine Maternal Serum Concentration	2.0 ng/mL Standard Deviation 1.0

PRIMARY outcome

Timeframe: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing

The half-life of amlodipine in the maternal plasma in the peripartum period was measured.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=11 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Half-life of Amlodipine in Maternal Plasma	13.7 Hours Standard Deviation 4.9

PRIMARY outcome

Timeframe: Maternal blood samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing

Population: Although 16 women were enrolled in the trial, only 11 had their blood drawn at the time of delivery due to limited availability of study personnel.

The clearance rate of amlodipine from the maternal plasma was measured.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=11 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Clearance Rate of Plasma Amlodipine	109.7 L/hr Standard Deviation 58.9

PRIMARY outcome

Timeframe: Pair maternal blood sample and cord blood sample will draw within 1 hour of delivery

Maternal and cord blood amlodipine levels/concentrations will be determined.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=11 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Drug Levels/Concentration in Cord Blood (Amlodipine Levels/Concentrations) Infant cord blood plasma amlodipine concentration	0.49 ng/mL Standard Deviation 0.29
Drug Levels/Concentration in Cord Blood (Amlodipine Levels/Concentrations) Maternal serum amlodipine concentration	1.27 ng/mL Standard Deviation 0.84

PRIMARY outcome

Timeframe: Breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 hours after amlodipine dosing

The concentration of amlodipine besylate was measured in breastmilk samples.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=6 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Amlodipine Concentration in Breastmilk	NA ng/mL Standard Deviation NA Amlodipine concentrations in maternal breast milk were undetectable at the lower limit of assay detection (\<0.1 ng/mL).

PRIMARY outcome

Timeframe: Infant blood sample drawn at approximately 36 hours of life

Population: Of the 16 patients enrolled in the study, only 8 continued in the study and allowed their infant's to have study sampling performed.

Infant amlodipine level/concentration will be determined.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=8 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Drug Level/Concentration in Infant Blood (Amlodipine Level/Concentration)	NA ng/mL Standard Deviation NA Amlodipine concentrations in infant plasma were undetectable at the lower limit of assay detection (\<0.1 ng/mL)

SECONDARY outcome

Timeframe: Neonatal weight at the time of birth.

The neonatal weight at birth was collected.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=16 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Neonatal Birth Weight	3281 grams Standard Deviation 525

SECONDARY outcome

Timeframe: Gestational age at the time of birth

The mean gestational age of infants born to mothers taking Amlodipine besylate 5 mg daily was collected.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=16 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Infant Gestational Age at Delivery.	38.2 weeks Standard Deviation 0.8

SECONDARY outcome

Timeframe: Time from birth to hospital discharge

The length of stay of infants born to women taking amlodipine besylate will be collected.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=16 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Infant Length of Stay.	3.6 Days Standard Deviation 0.5

SECONDARY outcome

Timeframe: During neonatal hospitalization

Any major complications experienced by infants born to women taking amlodipine besylate including NICU admission, intraventricular hemorrhage, neonatal seizures, need for respiratory support and apnea were collected.

Outcome measures

Outcome measures
Measure	Pregnant Women Taking Amlodipine n=16 Participants Women already taking amlodipine besylate 5 mg for treatment of chronic hypertension in pregnancy who plan to breastfeed postpartum will be assigned to the single experimental arm. Amlodipine besylate: Pregnant and postpartum women will continue taking amlodipine besylate 5 mg for treatment of chronic hypertension as prescribed by their clinician.
Major Infant Complications Admission to the NICU	0 Participants
Major Infant Complications Major neonatal complications (IVH, apnea, seizure)	0 Participants

Adverse Events

Pregnant Women Taking Amlodipine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Jamie Morgan, MD

University of Texas Southwestern Medical Center

Phone: 214-645-3838

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place