NCT06165146

A Study of the Effects of Pirtobrutinib (LOXO-305) on Repaglinide (CYP2C8 Substrate) in Healthy Participants

Completed Phase 1 Results posted Last updated 17 March 2025

What this trial tests

Phase 1 trial testing Repaglinide in Healthy in 16 participants. Completed in 30 December 2020.

Timeline

10 November 2020

Primary endpoint
30 December 2020

30 December 2020

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	basic science
Enrollment	16
Start date	10 November 2020
Primary completion	30 December 2020
Estimated completion	30 December 2020
Sites	1 location across United States

Drugs / interventions tested

• Repaglinide (repaglinide) — full drug profile →
• Pirtobrutinib — full drug profile →

Conditions studied

• Healthy — all drugs for Healthy →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

Adults 18 to 55, any sex, with Healthy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Repaglinide Primary · Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)

PK: AUC(0-t) of repaglinide was reported.

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	9.59	± 36.9
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	22.2	± 56.1

PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Repaglinide Primary · Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)

PK: AUC(0-inf) of repaglinide was reported.

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	9.79	± 36.5
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	22.5	± 55.7

PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Repaglinide Primary · Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)

PK: AUC-inf (%extrap) of repaglinide was reported.

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	1.94	± 41.8
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	1.10	± 60.6

PK: Maximum Observed Concentration (Cmax) of Repaglinide Primary · Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)

PK: Cmax of repaglinide was reported.

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	6.88	± 59.3
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	13.6	± 47.4

PK: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Repaglinide Primary · Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)

PK: Tmax of repaglinide was reported.

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	0.625	0.333 – 1.00
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	0.750	0.500 – 1.00

PK: Apparent Terminal Elimination Rate Constant (Lambda Z) of Repaglinide Primary · Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)

PK: Lambda Z of repaglinide was reported.

Participant 1

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	0.128
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	0.152

Participant 2

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	0.130
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	0.150

Participant 3

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	0.228
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	0.151

Participant 4

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	0.0847
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	0.157

Participant 5

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	0.0809
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	0.139

Participant 6

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	0.126
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	0.141

Participant 7

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	0.138
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	0.247

Participant 8

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	0.219
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	0.0995

PK: Apparent Systemic Clearance (CL/F) of Repaglinide Primary · Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)

PK: CL/F of repaglinide was reported.

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	51.1	± 36.5
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	22.2	± 55.7

PK: Apparent Plasma Terminal Elimination Half-life (t½) of Repaglinide Primary · Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)

PK: t½ of repaglinide was reported.

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	4.86	± 34.6
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	4.11	± 30.0

PK: Apparent Volume of Distribution (Vz/F) of Repaglinide Primary · Period 1, Day 1 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose); Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16 and 24 hours post-dose)

PK: Vz/F of repaglinide was reported.

Group	Value	95% CI
Period 1: 0.5 mg Repaglinide	358	± 39.3
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	131	± 66.0

PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib Primary · Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)

PK: AUC0-t of pirtobrutinib was reported.

Group	Value	95% CI
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	184000	± 22.1

PK: Area Under the Concentration-time Curve During a Dosing Interval (AUCtau) of Pirtobrutinib Primary · Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)

PK: AUCtau of pirtobrutinib was reported.

Group	Value	95% CI
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	105000	± 18.0

PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib Primary · Period 2, Day 12 (Pre-dose, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 24, 42, 78 and 100 hours post-dose)

PK: Cmax of pirtobrutinib was reported.

Group	Value	95% CI
Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide	7220	± 15.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 23 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Period 1: 0.5 mg Repaglinide

Serious: 0/16 (0%)

Deaths: 0/16

Period 2: 200 mg Pirtobrutinib QD

Serious: 0/16 (0%)

Deaths: 0/16

Period 2: 200 mg Pirtobrutinib QD + 0.5 mg Repaglinide

Serious: 0/16 (0%)

Deaths: 0/16

Other adverse events (8 terms — click to expand)

Reaction	System	Period 1: 0.5 mg Repaglinide	Period 2: 200 mg Pirtobrut…	Period 2: 200 mg Pirtobrut…
Petechiae	Skin and subcutaneous tissue disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Feeling abnormal	General disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Acne	Skin and subcutaneous tissue disorders	—	—	—

Data from ClinicalTrials.gov NCT06165146 adverse events section.

Sponsor's own description

The main purpose of this study is to evaluate the effect of pirtobrutinib (LOXO-305) on single oral dose of repaglinide (CYP2C8 substrate) when administered as multiple doses by conducting the blood tests to measure how much pirtobrutinib (LOXO-305) is in the bloodstream and how the body handles and eliminates pirtobrutinib (LOXO-305) in adult healthy participants. The study will also evaluate the safety and tolerability of pirtobrutinib (LOXO-305). The study is conducted in two periods. Participants will stay in this study for up to 54 days.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.