Healthy VolunteersPhase 1NCT01458769
Pharmacokinetics, Safety & Tolerability of Isotopologs of Atazanavir (ATV), With Pharmacokinetic Comparison to Reyataz
A Phase 1 study testing C-10276, C-10297 and C-10299 in people with Healthy Volunteers, run by Concert Pharmaceuticals.
Trial summary
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of isotopologs of Atazanavir both as single agents and as combinations. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- C-10276, C-10297 and C-10299
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- No sites listed yet
- Study dates
- Dec 2010to Apr 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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
About this study
Official title: 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.
Read the 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.
- Conditions
- Healthy Volunteers
- Being tested
- C-10276, C-10297, C-10299, Reyataz®
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C-10276Drug
C-10276 200 mg, C-10276 400 mg, Reyataz 400 mg oral, single dose
C-10276Drug
C-10276 300 mg, CTP-518 100 mg with C-10276 300 mg, C-10276 400 mg oral, single dose
C-10297Drug
C-10297 200 mg, oral, single dose
C-10299Drug
C-10299 200 mg, oral, single dose
C-10297Drug
C-10297 400 mg, Reyataz 400 mg, C-10297 600 mg, oral, single dose
C-10299Drug
C-10299 400 mg, Reyataz 400 mg, C-10299 600 mg, oral, single dose
C-10276Drug
C-10276 600 mg, Reyataz 400 mg, Reyataz 600 mg, oral, single dose
Reyataz®Drug
Reyataz 400 mg, oral, single dose Reyataz 600 mg, oral, single dose
| Study group | Role | What they receive |
|---|---|---|
| Part A1 | Active comparator | 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 Receives: Drug: C-10276 |
| Part A2 | Active comparator | 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) Receives: Drug: C-10276 |
| Part B Group 1 | Active comparator | Group B1 will evaluate single doses of an ATV isotopolog, C-10297.
C-10297 200 mg Receives: Drug: C-10297 |
| Part B Group 2 | Active comparator | Group B2 will evaluate single doses of an ATV isotopolog, C-10299.
C-10299 200 mg Receives: Drug: C-10299 |
| Part B Group 3 | Active comparator | 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 Receives: Drug: C-10297; Drug: Reyataz® |
| Part B Group 4 | Active comparator | 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 Receives: Drug: C-10299; Drug: Reyataz® |
| Part B Group 5 | Active comparator | 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 Receives: Drug: C-10276; Drug: Reyataz® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Profile of Pharmacokinetics
AUC, Cmax, C24
Measured: predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 30, 36,48 hours
Secondary outcomes (1)
Safety
Number of adverse events, change in laboratory parameters, changes from baseline in blood pressure and ECGs
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2011 (estimated)
- Study startDec 2010
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Concert Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sepehr Shakib, MD, Principal investigator, Adelaide, SA 5000 Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01458769
- Sponsor's protocol ID
- CP405.1003
- Status last verified
- May 2013
- First submitted
- 22 Jun 2011
- Last updated
- 24 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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®.
- ClinicalTrials.gov ID
- NCT01458769
- Acronym / sponsor ID
- CP405.1003
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Concert PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 25 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of isotopologs of Atazanavir both as single agents and as combinations.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part A1 | Active comparator | Drug: C-10276Part 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 |
| Part A2 | Active comparator | Drug: C-10276Part 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) |
| Part B Group 1 | Active comparator | Drug: C-10297Group B1 will evaluate single doses of an ATV isotopolog, C-10297. C-10297 200 mg |
| Part B Group 2 | Active comparator | Drug: C-10299Group B2 will evaluate single doses of an ATV isotopolog, C-10299. C-10299 200 mg |
| Part B Group 3 | Active comparator | Drug: C-10297, Drug: Reyataz®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 |
| Part B Group 4 | Active comparator | Drug: C-10299, Drug: Reyataz®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 |
| Part B Group 5 | Active comparator | Drug: C-10276, Drug: Reyataz®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 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| C-10276C-10276 200 mg, C-10276 400 mg, Reyataz 400 mg oral, single dose | Drug | Part A1 |
| C-10276C-10276 300 mg, CTP-518 100 mg with C-10276 300 mg, C-10276 400 mg oral, single dose | Drug | Part A2 |
| C-10297C-10297 200 mg, oral, single dose | Drug | Part B Group 1 |
| C-10299C-10299 200 mg, oral, single dose | Drug | Part B Group 2 |
| C-10297C-10297 400 mg, Reyataz 400 mg, C-10297 600 mg, oral, single dose | Drug | Part B Group 3 |
| C-10299C-10299 400 mg, Reyataz 400 mg, C-10299 600 mg, oral, single dose | Drug | Part B Group 4 |
| C-10276C-10276 600 mg, Reyataz 400 mg, Reyataz 600 mg, oral, single dose | Drug | Part B Group 5 |
| Reyataz®Reyataz 400 mg, oral, single dose Reyataz 600 mg, oral, single dose | Drug | Part B Group 3, Part B Group 4, Part B Group 5 |
Primary outcome
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
1 secondary outcome
Safety
Time frame: 3 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sepehr Shakib, MD principal investigator
Adelaide, SA 5000 Australia
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing C-10276, C-10297 and C-10299 in people with Healthy Volunteers, run by Concert Pharmaceuticals.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2013.