Clinical trial NCT03657290: A Study in Evaluating Bioequivalence of Test and Reference Vadadustat 450 MG and 150 MG Tablets and to Determine Food Effect on the 450 MG Tablet
Official title: A Randomized, Open-Label, Single-Dose, Three-Period Six-Sequence Crossover Study in Healthy Adults to Assess Bioequivalence Between Test and Reference Vadadustat 450 mg and 150 mg Tablets and to Determine Food Effect on the 450 mg Vadadustat Tablet.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Vadadustat
healthy volunteers
bioequivalence
pharmacokinetics
Lead sponsor: Akebia Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-09-05
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a randomized, open-label, single-dose, three-period, six- sequence crossover study in healthy adults. A total of 54 eligible subjects will be randomized to one of six treatment sequences (ABC, ACB, BAC, BCA, CAB, or CBA). Refer to Treatment Sequences below. Each sequence is comprised of 3 treatments
Primary purpose: TREATMENT

Brief summary: This is a healthy volunteers study to assess the bioequivalence of vadadustat 450 mg tablets (Test A) compared to three 150mg tablets (Reference B). The study will also assess the effect of food on the bioavailability of vadadustat 450 mg tablet.

Detailed description: This is a randomized, open-label, single-dose, three-period crossover study in healthy adults to assess the bioequivalence of 3 X 150 mg vadadustat tablets (Test) compared to a single 450 mg vadadustat tablet (reference). Blood samples for vadadustat PK will be collected at pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 18, 24, 32, 40, and 48 hours post-dose. The study will also assess the effect of food on vadadustat bioavailability by evaluating the pharmacokinetics of the 450 mg tablet in fed and fasted subjects.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects between ≥18 years and ≤55 years of age
* Healthy subjects per Investigator judgment as documented by the medical history, physical examination, vital sign assessments, 12-lead electrocardiogram (ECG), clinical laboratory assessments, and general observations.
* Have a body weight ≥50 kg and body mass index (BMI) ≥18.5 kg/m2 to 29.5 kg/m2 inclusive
* Understands the procedures, provides ICF and willing to comply with study requirements
* Willing and able to comply with the requirements of the study protocol.

Exclusion Criteria:

* Current or past history of cardiovascular, cerebrovascular, pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic, urologic, neurologic, dermatologic, psychiatric, or other major disease.
* History of cancer (except non- melanoma skin cancer) or history of chemotherapy use.
* Any surgical or medical condition or history that may potentially alter the absorption, metabolism, or excretion of study treatment, such as, but not limited to gastric bypass surgery or gastric or duodenal ulcers.
* History of severe allergic or anaphylactic reactions. Chronic daily medication use.
* History of drug abuse Excessive alcohol consumption.
* Smoking and the use of nicotine-containing products
* Consumption of grapefruit or grapefruit juice, pomelo, star fruit, Seville or Moro (blood) orange, or their associated products
* Participation in another clinical trial or exposure to any investigational agent.
* Donation of blood or significant blood loss or plasma donation.
* Any condition that would interfere with the ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the patient at undue risk.

Primary outcomes:
measure: Bioequivalence - Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast)
timeFrame: Baseline visit, 48 hours
measure: Bioequivalence - Area under plasma concentration-time curve from 0 to infinity (AUCinf)
timeFrame: Baseline visit, 48 hours
measure: Bioequivalence - Area under plasma concentration-time curve from 0 to last sampling point (AUCall)
timeFrame: Baseline visit, 48 hours
measure: Bioequivalence - Observed Maximum concentration (Cmax)
timeFrame: Baseline visit, 48 hours
measure: Measure Food Effect - Area under plasma concentration-time curve from 0 to last quantifiable concentration (AUClast)
timeFrame: Baseline visit, 48 hours
measure: Measure Food Effect - 2. Area under plasma concentration-time curve from 0 to infinity (AUCinf)
timeFrame: Baseline visit, 48 hours
measure: Measure Food Effect - 2.3. Observed Maximum concentration (Cmax)
timeFrame: Baseline visit, 48 hours
Secondary outcomes:
measure: Time to reach Cmax
timeFrame: Baseline visit, 48 hours
measure: Time to reach Tmax
timeFrame: Baseline visit, 48 hours
measure: Mean residence time (MRT)
timeFrame: Baseline visit, 48 hours
measure: Elimination rate constant (Kel)
timeFrame: Baseline visit, 48 hours
measure: Apparent total body clearance (CL/F)
timeFrame: Baseline visit, 48 hours
measure: Apparent volume of distribution (Vd/F)
timeFrame: Baseline visit, 48 hours
measure: Terminal half-life (t1/2)
timeFrame: Baseline visit, 48 hours
measure: Percentage of extrapolated area under the curve from time t to infinity (AUCextrap or Residual Area)
timeFrame: Baseline visit, 48 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Paraxel International
state: Maryland
Study officials:
affiliation: Sponsor GmbH
name: Akebia Therapeutics
role: STUDY_DIRECTOR
References: