The effect of antacid and mineral supplements on bictegravir pharmacokinetics: results from a Phase 1, open-label, drug-drug interaction study.

Co-administration of bictegravir with aluminum/magnesium-containing antacid under fasted conditions reduced BIC AUC by 79%.

• BIC exposure (area under the plasma concentration-time curve extrapolated to infinity) was reduced by 79% when co-administered with maximum-strength aluminum/magnesium-containing antacid under fasted conditions.
• The study was an open-label, single-dose, Phase 1 study in adult participants without HIV (N=42 enrolled).
• BIC was administered as part of the single-tablet combination B/F/TAF (bictegravir/emtricitabine/tenofovir alafenamide).
• Pharmacokinetic parameters were compared using analysis of variance to calculate geometric least-squares mean ratios and 90% confidence intervals.

Co-administration of bictegravir with calcium carbonate under fasted conditions reduced BIC AUC by 33%.

• BIC exposure (AUC extrapolated to infinity) was reduced by 33% when co-administered with calcium carbonate under fasted conditions.
• This interaction was less severe than that observed with aluminum/magnesium-containing antacid (79% reduction) or ferrous fumarate (63% reduction).
• Co-administration of B/F/TAF with calcium carbonate with a meal reduced the impact of the interaction.
• The study enrolled 42 participants across all treatment conditions.

Co-administration of bictegravir with ferrous fumarate under fasted conditions reduced BIC AUC by 63%.

• BIC exposure (AUC extrapolated to infinity) was reduced by 63% when co-administered with ferrous fumarate under fasted conditions.
• This represents a substantial chelation-type drug-drug interaction mediated by iron cations.
• Co-administration of B/F/TAF with ferrous fumarate with a meal reduced the impact of the interaction.
• The mechanism of interaction involves chelation of metal cations with bictegravir, consistent with the known mechanism of action of integrase strand transfer inhibitors involving binding to magnesium ions.

Taking B/F/TAF with a meal mitigated the drug-drug interactions with calcium carbonate and ferrous fumarate.

• Co-administration of B/F/TAF with calcium carbonate or ferrous fumarate with a meal reduced the impact of the interactions compared to fasted co-administration.
• Fed conditions reduced the 33% AUC reduction seen with calcium carbonate and the 63% reduction seen with ferrous fumarate under fasted conditions.
• This strategy was identified as one of the effective approaches for combined use of BIC with metal cation-containing medications.

Administering B/F/TAF 2 hours before aluminum/magnesium-containing antacid reduced the impact of the chelation interaction.

• Administration of B/F/TAF 2 hours before the antacid was identified as an effective strategy to mitigate chelation effects on BIC exposure.
• The study assessed BIC pharmacokinetics when B/F/TAF was administered 2 hours before or after the antacid as alternative dosing strategies.
• Administration 2 hours before the aluminum/magnesium-containing antacid is recommended as a mitigation strategy for patients who require concomitant use.

B/F/TAF was well tolerated alone and in combination with all metal cation-containing medications studied.

• B/F/TAF was well tolerated alone or in combination with aluminum/magnesium-containing antacid, calcium carbonate, and ferrous fumarate.
• The study was conducted in 42 adult participants without HIV.
• No notable safety signals were identified across the various co-administration conditions including fasted, fed, and staggered dosing.

The study design evaluated multiple co-administration strategies including fasted, fed, and staggered dosing conditions.

• This was an open-label, single-dose, Phase 1 study registered at NCT05502341/NCT06333808.
• The study enrolled 42 adult participants without HIV.
• Conditions evaluated included co-administration under fasted conditions, fed conditions, and administration of B/F/TAF 2 hours before or after the antacid.
• Metal cation-containing medications tested included maximum-strength aluminum/magnesium-containing antacid, calcium carbonate, and ferrous fumarate.
• Pharmacokinetic parameters were compared using analysis of variance to calculate geometric least-squares mean ratios and 90% confidence intervals.