Pharmacokinetics, Safety & Tolerability of Isotopologs of Atazanavir (ATV), With Pharmacokinetic Comparison to Reyataz

May 23, 2013 updated by: Concert Pharmaceuticals

Open-labeled, Randomized, Crossover, Single-dose Study in Healthy Male Subjects to Evaluate the Pharmacokinetics, Safety & Tolerability of Stable Isotopologs of Atazanavir (ATV), Administered as Single Agents or as Combinations of Two Isotopologs, With a Pharmacokinetic Comparison to Reyataz®.

The purpose of this study is to assess the safety, tolerability and pharmacokinetics of isotopologs of Atazanavir both as single agents and as combinations.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

There are two parts to this study. Part A is a three-period, crossover design. Eligible subjects will be randomized to 1 of 4 sequences, in groups of 4 subjects each. All study drug doses, including the comparator, Reyataz, will be administered as single, open-labeled doses to subjects after a light meal. There will be a 7-day washout between individual subjects doses; that is, dosing will occur on the same day each week.

Part B evaluations are based on the results of Part A. Part B will further consist of two subparts. In the first subpart, low single doses of 2 new isotopologs will be dosed to two groups of 4 subjects each, B1 and B2, respectively. Following assessment of safety and pharmacokinetics in the first subpart, the second subpart, which consists of three groups of 8 subjects (B3, B4, B5) each will be dosed. Subjects enrolled in B3, B4, and B5 will participate in a 3-way partial crossover study design.

The objectives will be to compare the PK properties, in healthy male subjects after a light meal, of single oral doses of single agent ATV isotopologs or as combinations of two ATV isotopologs with the PK properties in the same subjects, after a light meal, of a single dose of either 400 mg or 600 mg Reyataz. The safety and tolerability will also be evaluated.

Blood samples for pharmacokinetic analysis will be collected. Actual dosing and sampling times will be used for analysis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
47

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Healthy, as determined by the responsible physician, based on a medical evaluation including history, physical examination, vital signs, electrocardiograms (ECGs) and laboratory tests assessed at the screening visit and prior to the first dose of study drug. A subject with a non-clinically significant abnormality or laboratory parameters outside the reference range may be included only if the investigator considers that the finding will not compromise the subject's safety and will not interfere with the study procedures or data interpretation.
  • Healthy adult males between 18 and 50 years of age, inclusive
  • Body weight ≥ 50 kg and BMI within the range of 18 to 32 kg/m2, inclusive, at screening
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and the protocol
  • Willing and able to be confined at the clinical research center for the study days
  • Negative tests for selected drugs of abuse, cotinine, and alcohol at screening and Day -1
  • Dietary habits that fall within the range of normal, as determined by the investigator. Examples of unusual diets are liquid diets, protein-only diets, high fat-diets, or low-carbohydrate diets.
  • Willingness of male subjects to abstain from sexual intercourse with pregnant or lactating women; and if engaging in sexual intercourse with a female partner who could become pregnant, a willingness of male subjects to use a condom and spermicide, in addition to having the female partner use another form of contraception such as an intrauterine device, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation. This criterion must be followed from the time of first study drug administration until 30 days after the final administration of study drug.

Exclusion Criteria:

  • History of clinically significant central nervous system (eg, seizures), cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal (GI) conditions; or history of such conditions that, in the opinion of the investigator, may place the subject at an unacceptable risk as a participant in this trial, may interfere with the interpretation of safety and/or tolerability data obtained in the trial, or may interfere with the absorption, distribution, metabolism, or excretion of the study drugs
  • PR interval ≥ 220 msec or QRS duration ≥ 120 msec or QT interval > 450 msec obtained at screening visit or prior to the first dose of study drug
  • Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), serum creatinine, or bilirubin > upper limit of normal (ULN) at screening or prior to the first dose of study drug. These laboratory tests may be repeated once, if they are abnormal on first screening, and if there is a medical reason to believe the results may be inaccurate. If the repeat test is within the reference range, the subject may be included only if the investigator considers that the previous finding will not compromise the subject's safety and will not interfere with the interpretation of safety data.
  • Positive blood screen for human immunodeficiency virus (HIV antibody), hepatitis B virus surface antigen, or hepatitis C virus antibody at screening
  • Urinalysis positive for protein or glucose (greater than trace findings of protein or glucose) at screening or prior to the first dose of study drug
  • History of drug abuse within 6 months of screening
  • History of any tobacco product use within 3 months prior to the study, to be verified by a urine cotinine screen of < 200 ng/mL at screening and prior to the first dose of study drug
  • Participation in a clinical trial and receipt of an investigational medication or a new chemical entity within 30 days, 5 half-lives, or twice the duration of the biological effect of any medication (whichever is longer) prior to the first dose of current study drug
  • Use of prescription or non-prescription medications, including herbal and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study drug, or use of St. John's Wort within 14 days prior to the first dose of study drug. (The subject may take paracetamol (≤ 2 grams/day) or ibuprofen (≤ 1600 mg/day) for up to 48 hours prior to the first dose of study drug. The investigator and study team may review medication use on a case-by-case basis to determine if its use would compromise subject safety or interfere with study procedures or data interpretation.)
  • Consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges, or red wine within 7 days prior to administration of study drug
  • Consumption of any caffeine and/or xanthine products (ie, coffee, tea, chocolate and caffeine containing sodas, colas, etc) within 48 hours prior to each dose of study drug and while confined at the clinical site
  • Donation of blood or blood products or blood collection in excess of 470 mL within 8 weeks prior to dosing
  • History of sensitivity to any of the study drugs or components thereof, or a history of medication allergy or other allergy that, in the opinion of the investigator, contraindicates study participation
  • Unwillingness to comply with protocol-specified lifestyle and/or dietary restrictions
  • Major surgery within 4 weeks of screening
  • Uncontrolled intercurrent illness (ie, active infection)
  • Any other medical or psychiatric illness that could, in the investigator's opinion, compromise the subject's safety or interfere with the completion of this protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Part A1

Part A1 will evaluate two single ascending doses of the single agent C-10276 (an ATV isotopolog), and a dose of Reyataz.

C-10276 200 mg -> C-10276 400 mg -> Reyataz 400 mg

C-10276 200 mg -> Reyataz 400 mg -> C-10276 400 mg
Drug: C-10276
C-10276 200 mg, C-10276 400 mg, Reyataz 400 mg oral, single dose
Drug: C-10276
C-10276 300 mg, CTP-518 100 mg with C-10276 300 mg, C-10276 400 mg oral, single dose
Drug: C-10276
C-10276 600 mg, Reyataz 400 mg, Reyataz 600 mg, oral, single dose
Active Comparator: Part A2

Part A2 will evaluate the single agent C-10276, co-administration of CTP-518 and C-10276, and a dose of Reyataz.

C-10276 300 mg -> Co-dose Ratio 1 CTP-518 (100 mg) with C-10276 (300 mg)-> C-10276 400 mg

C-10276 300 mg -> C-10276 400 mg -> Co-dose Ratio 1 CTP-518 (100 mg) with C-10276 (300 mg)
Drug: C-10276
C-10276 200 mg, C-10276 400 mg, Reyataz 400 mg oral, single dose
Drug: C-10276
C-10276 300 mg, CTP-518 100 mg with C-10276 300 mg, C-10276 400 mg oral, single dose
Drug: C-10276
C-10276 600 mg, Reyataz 400 mg, Reyataz 600 mg, oral, single dose
Active Comparator: Part B Group 1

Group B1 will evaluate single doses of an ATV isotopolog, C-10297.

C-10297 200 mg
Drug: C-10297
C-10297 200 mg, oral, single dose
Drug: C-10297
C-10297 400 mg, Reyataz 400 mg, C-10297 600 mg, oral, single dose
Active Comparator: Part B Group 2

Group B2 will evaluate single doses of an ATV isotopolog, C-10299.

C-10299 200 mg
Drug: C-10299
C-10299 200 mg, oral, single dose
Drug: C-10299
C-10299 400 mg, Reyataz 400 mg, C-10299 600 mg, oral, single dose
Active Comparator: Part B Group 3

Group B3 will evaluate two single ascending doses of isotopologs C-10297 and 400 mg dose of Reyataz in a 3-way crossover design.

C-10297 400 mg -> Reyataz 400 mg -> C-10297 600 mg
Drug: C-10297
C-10297 200 mg, oral, single dose
Drug: C-10297
C-10297 400 mg, Reyataz 400 mg, C-10297 600 mg, oral, single dose
Drug: Reyataz®
Reyataz 400 mg, oral, single dose Reyataz 600 mg, oral, single dose
Active Comparator: Part B Group 4

Group B4 will evaluate two single ascending doses of isotopolog C-10299 and a 400 mg dose of Reyataz in a 3-way crossover design.

C-10299 400 mg -> Reyataz 400 mg -> C-10299 600 mg
Drug: C-10299
C-10299 200 mg, oral, single dose
Drug: C-10299
C-10299 400 mg, Reyataz 400 mg, C-10299 600 mg, oral, single dose
Drug: Reyataz®
Reyataz 400 mg, oral, single dose Reyataz 600 mg, oral, single dose
Active Comparator: Part B Group 5

Group B5 will evaluate a single dose of C-10276 and a 400 and 600 mg dose of Reyataz in a 3-way crossover design.

C-10276 600 mg -> Reyataz 400 mg -> Reyataz 600 mg
Drug: C-10276
C-10276 200 mg, C-10276 400 mg, Reyataz 400 mg oral, single dose
Drug: C-10276
C-10276 300 mg, CTP-518 100 mg with C-10276 300 mg, C-10276 400 mg oral, single dose
Drug: C-10276
C-10276 600 mg, Reyataz 400 mg, Reyataz 600 mg, oral, single dose
Drug: Reyataz®
Reyataz 400 mg, oral, single dose Reyataz 600 mg, oral, single dose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Profile of Pharmacokinetics
Time Frame: predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36,48 hours
AUC, Cmax, C24
predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36,48 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: 3 days
Number of adverse events, change in laboratory parameters, changes from baseline in blood pressure and ECGs
3 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Concert Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sepehr Shakib, MD, Adelaide, SA 5000 Australia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 22, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 25, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 24, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 23, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CP405.1003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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