Dataset Information

Coadministration of the prostaglandin F2? receptor antagonist preterm labour drug candidate OBE022 with magnesium sulfate, atosiban, nifedipine and betamethasone.

ABSTRACT:

Aims

To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development.

Methods

Part A: open-label, randomized, 3-period crossover assessing coadministration of single doses of OBE022 (1100 mg) and MgSO₄ . Part B: open-label, single-sequence crossover assessing the interactions following administration of OBE022 (1000 mg/day) at steady state coadministered with single doses of atosiban, nifedipine and betamethasone. Twenty-five healthy nonpregnant women of reproductive age were enrolled (Part A: n = 12; Part B: n = 13).

Results

OBE022, alone or in combination with standard-of-care medications, was well tolerated. Headache and dizziness were the most frequently reported adverse events; dizziness occurred more often with the nifedipine/OBE022 combination. There were no clinically significant pharmacokinetic interactions when coadministered with MgSO₄ . Co-administration had no notable effect on atosiban exposure. Atosiban reduced exposure to OBE002 (peak concentration [C_max ] 22%, area under the concentration-time curve [AUC] 19%). Coadministration with betamethasone slightly increased betamethasone exposure (C_max + 18%, AUC +27%) and OBE002 exposure (C_max + 35%, AUC +15%). These changes were not considered clinically significant. Coadministration with nifedipine slightly increased OBE002 exposure (C_max + 29%, AUC +24%) and markedly increased nifedipine exposure (C_max by 2-fold and AUC by 2-fold), which may be clinically significant.

Conclusions

The use of OBE022, a PGF2? antagonist prodrug, in combination with standard-of-care medicines may provide new treatment alternatives for preterm labour. All tested combinations were well tolerated. Nifedipine doses could potentially be reduced or staggered when coadministered with OBE022.

SUBMITTER: Pohl O

PROVIDER: S-EPMC6595366 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Coadministration of the prostaglandin F2α receptor antagonist preterm labour drug candidate OBE022 with magnesium sulfate, atosiban, nifedipine and betamethasone.

Pohl Oliver O Marchand Line L Gotteland Jean-Pierre JP Coates Simon S Täubel Jörg J Lorch Ulrike U

British journal of clinical pharmacology 20190511 7

<h4>Aims</h4>To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development.<h4>Methods</h4>Part A: open-label, randomized, 3-period crossover assessing coadministration of single doses of OBE022 (1100 mg) and MgSO<sub>4</sub> . Part B: open-label, single-sequence crossover assessing the interactions following administrati ...[more]

PMID: 30891820

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