Safety, Tolerability and Pharmacokinetics of Escalating Single Doses of ENV8058 (TAK-058) in Healthy Participants

NCT02153099 | Completed Phase 1 Results

• 2 other identifiers: ENV8058_101U1111-1154-9569
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to characterize the safety and tolerability profile of escalating dose levels of ENV8058 (TAK-058) solution when administered as a single oral dose in healthy adults.

Conditions

Dose Finding Study

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)

  Treatment-emergent adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 14 days after the last dose of study drug, or if a serious adverse event, within 30 days after the last dose of study drug.

  Baseline up to Day 30

• Percentage of Participants With Markedly Abnormal Safety Laboratory Tests

  The percentage of participants with any markedly abnormal standard safety laboratory values, including hematology, serum chemistries, and urinalysis, during the treatment period.

  Baseline up to Day 14

• Percentage of Participants With Markedly Abnormal Vital Sign Measurements

  The percentage of participants who meet markedly abnormal criteria for vital signs, including oral body temperature, respiration rate, pulse \[beats per minute (bpm)\], and resting blood pressure and after standing.

  Baseline up to Day 14

Secondary Outcomes (4)

• Cmax: Maximum Observed Plasma Concentration for ENV8058 (TAK-058)

  Predose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours postdose

• AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for ENV8058 (TAK-058)

  Predose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours postdose

• AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for ENV8058 (TAK-058)

  Predose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours postdose

• Terminal Elimination Half-life (T1/2) Pharmacokinetic Parameter for ENV8058 (TAK-058)

  Predose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours postdose

Study Arms (7)

Cohort 1: TAK-058 15 mg

EXPERIMENTAL

TAK-058 15 mg, 100 mL oral solution, once on Day 1.

Drug: TAK-058 (ENV8058)

Cohort 2: TAK-058 30 mg

EXPERIMENTAL

TAK-058 30 mg, 100 mL oral solution, once on Day 1.

Drug: TAK-058 (ENV8058)

Cohort 3: TAK-058 45 mg

EXPERIMENTAL

TAK-058 45 mg, 100 mL oral solution, once on Day 1.

Drug: TAK-058 (ENV8058)

Cohort 4: TAK-058 5 mg

EXPERIMENTAL

TAK-058 5 mg, 100 mL oral solution, once on Day 1.

Drug: TAK-058 (ENV8058)

Cohort 5: TAK-058 75 mg

EXPERIMENTAL

TAK-058 75 mg, 100 mL oral solution, once on Day 1.

Drug: TAK-058 (ENV8058)

Cohort 6: TAK-058 150 mg

EXPERIMENTAL

TAK-058 150 mg, 100 mL oral solution, once on Day 1.

Drug: TAK-058 (ENV8058)

Cohort 1-6: Placebo

PLACEBO COMPARATOR

TAK-058 placebo-matching, 100 mL oral solution, once on Day 1.

Drug: Placebo

Interventions

TAK-058 (ENV8058) DRUG

TAK-058 (ENV8058) oral solution

Cohort 1: TAK-058 15 mg; Cohort 2: TAK-058 30 mg; Cohort 3: TAK-058 45 mg; Cohort 4: TAK-058 5 mg; Cohort 5: TAK-058 75 mg; Cohort 6: TAK-058 150 mg

Placebo DRUG

TAK-058 (ENV8058) placebo-matching oral solution

Cohort 1-6: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations.
• Is a healthy male or female adult who is 18 to 55 years of age inclusive at the time of informed consent and study drug dosing.
• Weighs at least 45 kg (99 lbs) and has a body mass index (BMI) between 18.0 and 30.0 kg/m\^2, inclusive at Screening.
• A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
• A female participant with no childbearing potential, defined as the participant has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2 years and follicle-stimulating hormone (FSH)\>40 IU/L).

You may not qualify if:

• Has received any investigational compound within 30 days prior to the first dose of study medication.
• Is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
• Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the participant to participate or potentially confound the study results.
• Has a known hypersensitivity to any component of the formulation of ENV8058 (TAK-058).
• Has a positive urine drug result for drugs of abuse at Screening or Check-in (Day -1).
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• Has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table.
• If female, the participant is of childbearing potential (e.g premenopausal, not sterilized).
• If male, the participant intends to donate sperm during the course of this study or for 12 weeks thereafter.
• Has evidence of current cardiovascular, central nervous system, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking ENV8058 (TAK-058), or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to seizure disorders and cardiac arrhythmias.
• Has previously had a seizure or convulsion (lifetime), including absence seizure and febrile convulsion.
• Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, any surgical intervention known to impact absorption \[eg, bariatric surgery or bowel resection\], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent \[more than once per week\] occurrence of heartburn).
• Has a history of cancer or other malignancy, except basal cell carcinoma that has been in remission for at least 5 years prior to Day 1.
• Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or a known history of human immunodeficiency virus infection at Screening.
• Has used nicotine-containing products (including but not limited to cigarettes, electronic cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in (Day -1). Cotinine test is positive at Screening or Check-in (Day -1).

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Austin, Texas, United States

Location

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: May 29, 2014
• First Posted: June 2, 2014
• Study Start: June 1, 2014
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: December 17, 2015
• Results First Posted: December 17, 2015

Record last verified: 2015-11

Locations

US (1)