A Multiple Ascending Oral Dose Evaluation of the Safety, Tolerability, and Pharmacokinetics of DSP-1053 and Its Metabolites in Healthy Subjects and in Subjects With Major Depressive Disorder

NCT01774747 | Terminated Phase 1

• 1 other identifier: D7750090
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

Double-blind, placebo-controlled, multiple ascending oral dose evaluation of the safety, tolerability, and pharmacokinetics of DSP 1053 and its metabolites in healthy subjects and in subjects with major depressive disorder

Conditions

Healthy

Keywords

Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• To reach minimumally intolerable dose based on stopping criteria

  * At least 50% of subjects within a cohort at dose level experience multiple moderate drug related adverse events or one severe drug-related adverse event * one drug related serious adverse event within a cohort at dose level * seizure of any severity or seriousness is observed in a subject who received DSP-1053 * Mean plasma DSR\_22898 Cmax greater or equal to 32ng/ml for a cohort

  14 days

Secondary Outcomes (2)

• Characterize the pharmacodynamic relationship based on serotonin transporter occupancy of DSP-1053 following multiple oral doses of DSP-1053 in healthy subjects and major depressive disorder subjects

  14 days

• To characterize exposure of DSP-1053 and its metabolites (AUC, Cmax and Tmax) after multiple ascending dose of DSP-1053

  14 days

Study Arms (2)

DSP-1053

EXPERIMENTAL

DSP-1053 10, 15, 20, 30, 45, 60, 90 mg once daily for 14 days

Drug: DSP-1053; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Placebo 10, 15, 20, 30, 45, 60, 90 mg once daily for 14 days

Drug: DSP-1053; Drug: Placebo

Interventions

DSP-1053 DRUG

DSP-1053 10, 15, 20, 30, 45, 60, 90 mg once daily for 14 days

DSP-1053; Placebo

Placebo DRUG

Placebo 10, 15, 20, 30, 45, 60, 90 mg once daily for 14 days

DSP-1053; Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Subjects:
• Be able to understand and willing to sign the Informed Consent Form, and capable of providing written authorization for use and disclosure of protected health information per requirements of 45 Code of Federal Regulations (CFR) 164.508 (Health Information Portability and Accountability Act \[HIPAA\]).
• Be healthy male or female subjects between 18 and 50 years of age (inclusive). Have a BMI 18 and 33 kg/m2. Have no clinically relevant abnormal laboratory values at screening and Day -1.
• Have no clinically relevant findings from vital sign measurements at screening and check-in.
• Have no clinically relevant findings from physical examination at screening and check in.
• Have a negative urine drug of abuse test (cannabinoids, barbiturates, cocaine, opiates, benzodiazepines, phencyclidine, and methadone) and negative cotinine test at screening and check in.
• Have a negative alcohol breath test at screening and check in. Have a negative Hepatitis B surface antigen, Hepatitis C antibody, and human immunodeficiency virus (HIV) antibody tests at screening.
• Have normal hepatic function \[aspartate transaminase (AST), bilirubin, and alanine transaminase (ALT)\] and renal function (creatinine clearance greater than 80 mL/min as assessed by Cockcroft Gault equation using serum creatinine) at screening and Day 1.
• Be females who are of childbearing potential:
• have a negative serum hCG pregnancy test at screening and Day -1; willing to not breastfeed from Day -5 until 90 days after discharge from the study site;
• Be females who are:
• unable to have children (eg, post menopausal, tubal ligation, hysterectomy) OR willing to remain abstinent (not engage in sexual intercourse) from check in until 90 days after discharge from the study site.
• OR willing to use an effective method of double-barrier birth control (eg, partner using condom and female using diaphragm, contraceptive sponge, spermicide, or intrauterine device) from check-in until 90 days after discharge from the study site.
• Be males who:
• are sterile or willing to remain sexually abstinent or use an effective method of birth control (eg, condom) from check-in until 90 days after discharge from the study site.

You may not qualify if:

• Healthy Subjects
• Significant history or clinical manifestations of any acute or chronic condition that in the opinion of the PI, would limit the subject's ability to complete and/or participate in the study:
• metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders; drug hypersensitivity; stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (appendectomy, hernia repair, and/or cholecystectomy will be allowed at the discretion of the PI); abnormal ECG, which, in the PI's opinion, is clinically significant; known or suspected alcohol or substance abuse/ dependence within one year prior to check in; movement disorders including tremor; lifetime or family history of seizures or a febrile seizure. Poor peripheral venous access. Does not tolerate venipuncture. Donation of blood from 28 days prior to screening through study completion, inclusive.
• Receipt of blood products within 2 months prior to check in. Any acute or chronic condition that, in the opinion of the PI, would limit the subject's ability to complete and/or participate in this clinical study.
• Female subjects with menstrual dysfunction. Considered by the PI to be at imminent risk of suicide or injury to self, others, or property.
• Subject answers "yes" to "Suicidal Ideation" Items 4 or 5 on the CSSRS at screening.
• Subjects who, by history, have smoked or used tobacco products within 60 days from screening until study follow up.
• Consumption of food or beverages containing alcohol, grapefruit, or caffeine within 72 hours prior to check in and until discharge from the study site, unless deemed acceptable by the PI.
• Participation in any other investigational study drug trial in which receipt of an investigational study drug occurred within 5 half lives or 3 months prior to check-in, whichever is longer.
• Taken any drug(s) known to be clinically relevant cytochrome P450 2D6 (CYP2D6), or cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 28 days prior to the first DSP 1053 dose and during the study conduct through follow up.
• Taken any antihistamines within 14 days prior to check-in and during the study. Family history of prolonged QT interval (QTc) prolongation. Subjects, who by history, are at any risk for bleeding or have abnormal prothrombin values or currently use of anticoagulant treatment (such as warfarin) Clinically important folic acid or B12 abnormalities detected within 3 months before screening.
• Use of any prescription medications/products within 14 days prior to check in unless deemed acceptable by the PI.
• Subjects with MDD
• History of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, eating disorder, or obsessive compulsive disorder.
• Any current Axis I disorder other than major depressive disorder which is the focus of treatment.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (1)

California Clinical Trials Medical Group

Glendale, California, 91206, United States

Location

Study Officials

• Medical Director, DSP-1053

  Sumitomo Pharma America, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2013
• First Posted: January 24, 2013
• Study Start: December 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: June 18, 2014

Record last verified: 2014-06

Locations

US (1)