Multiple Ascending Dose Study on Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects or Subjects With Schizophrenia or Schizoaffective (MAD)

Amgen

Status and phase: Completed; Phase 1

Conditions: Schizophrenia or Schizoaffective Disorder

Treatments: Drug: Midazolam; Drug: AMG 581; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02504476

20130259

Details and patient eligibility

About

The purpose of this study is to find out the time it takes to absorb, distribute, breakdown and remove the drug from the body in healthy participants and subjects with schizophrenia and whether it causes any side effects.

Full description

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic profile of ascending multiple oral doses of AMG 581 in healthy subjects or subjects with schizophrenia or schizoaffective disorder on antipsychotic medication. The study will also assess the effects of AMG 581 on midazolam PK in healthy subjects or subjects with schizophrenia or schizoaffective disorder on antipsychotic medication.

Enrollment: 52 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Provided informed consent prior to initiation of any study-specific activities/procedures; -male or female subjects should be between the ages of 18 and 45 years (18-55 years for subjects with schizophrenia);-non-nicotine or non-tobacco (healthy subjects only); - no history of relevant medical disorders; - BMI ≥ 18.0; - females of non-reproductive potential; - males practicing effective birth control; - avoid tanning/direct sunlight; - schizophrenia or schizoaffective disorder; PANSS score ≤ 4 points on following items (i.e. conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution, hostility, depression, anxiety, disorientation, uncooperativeness, disturbance of volition, and poor impulse control) / total score ≤ 80 points

Exclusion criteria

• females lactating/breastfeeding; pregnant partners of male subjects; essential tremor or gait disturbance; - history of hereditary shorten QT syndrome; - malignancy or tumor (other than skin cancers); - history of GI disease that could interfere with absorption; - QTc ≥ 450 msec or ≤ 380 msec; - HbA1c ≥ 7%;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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52 participants in 9 patient groups, including a placebo group

AMG 581 - Dose 1

Active Comparator group

Treatment:

Drug: AMG 581

AMG 581 - Dose 2

Active Comparator group

Treatment:

Drug: AMG 581

AMG 581 - Dose 3

Active Comparator group

Treatment:

Drug: AMG 581

AMG 581 - Dose 4

Active Comparator group

Treatment:

Drug: AMG 581

Placebo - Dose 1

Placebo Comparator group

Treatment:

Drug: Placebo

Drug: AMG 581

Placebo - Dose 2

Placebo Comparator group

Treatment:

Drug: Placebo

Placebo - Dose 3

Placebo Comparator group

Treatment:

Drug: Placebo

Placebo - Dose 4

Placebo Comparator group

Treatment:

Drug: Placebo

AMG 581/Midazolam - Drug Interaction

Other group

Treatment:

Drug: Midazolam

Drug: AMG 581