Conditions: Healthy Subjects
Keywords: Non-randomized Verapamil Itraconazole Diltiazem Safety Tolerability Pharmacokinetics
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 15
Healthy volunteers: yes

Brief summary:
This is a phase 1, non-randomized, fixed sequence, 3-period, drug-drug interaction study to assess the pharmacokinetics (PK) of AZD7986 in healthy subjects when administered alone and in combination with multiple doses of verapamil and itraconazole or diltiazem

Detailed description:
This study will be an open-label, non-randomised, fixed sequence, 3-period study conducted at a single study centre to assess the PK of AZD7986 in healthy subjects when administered alone and in combination with multiple doses of verapamil and itraconazole or diltiazem. An adaptive design with an interim analysis of the PK data from Periods 1 and 2 will be used to determine which of itraconazole or diltiazem will be administered in combination with AZD7986 in Period 3.

Treatments to be administered in a fixed order separated by a washout period:

period 1 - single AZD7986 (25 mg) on Day 1 (1 hour before food), washout 7 days period 2 - verapamil (240 mg extended release formulation) daily 1 hour before food (Day 1 to 10) and a single dose of AZD7986 (25 mg) 1 hour before food (Day 5), washout period 14 days period 3 - subject to interim pharmacokinetic analysis of AZD7986 alone compared with AZD7986 and verapamil combined, either itraconazole (200 mg, oral solution formulation 10mg/mL) administered twice on Day 1 and daily on days 2 to 11 (1 hour before food) plus AZD7986 (25mg) single dose on Day 6 (1 hour before food); or diltiazem (360 mg, extended release formulation) on Days 1 to 13 (1 hour before food) plus AZD7986 (25 mg) 1 hour before food on Day 8.

Arms:
arm 1: AZD7986 (15 mg/mL) 25 mg dosage administered alone arm 2: Daily administration of verapamil (240 mg, extended release formulation) on Days 1 to 10 plus administration of single dose AZD7986 (25 mg) on Day 5 arm 3: Itraconazole (200 mg, oral solution formulation 10 mg/mL) administered twice on Day 1 and then daily Days 2 to 11 plus single dose AZD7986 (25 mg, tbc) on Day 6 arm 4: Diltiazem (360 mg, extended release formulation) administered Days 1 to 13 plus single dose AZD7986 (25 mg) on Day 8

Interventions: intervention 1: AZD7986 intervention 2: Verapamil intervention 3: Itraconazole intervention 4: Diltiazem
Intervention descriptions: intervention 1: Oral solution, single dose, dilution from concentrate intervention 2: Extended release tablet for oral use intervention 3: Oral solution intervention 4: Extended release capsule

Protocol document: