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Metabolic, CardiovascularPhase 1NCT01793870

A Study in Healthy Volunteers to Evaluate the Application of Stable Isotope Approach to Reduce Number of Subjects Needed for PK Studies

A Phase 1 study testing Tab carvedilol 25 mg, Tab carvedilol 6.25 mg and Powder carvedilol up to 2.5 mg in people with Metabolic, Cardiovascular, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This will be a randomized, open-label, single dose, 4-period, period balanced, crossover study. There will be at least 5 days between dosing in each session. The study consists of Screening period (30 days prior to Day 1), Treatment period consisting of 4 dosing periods (Day 1 is the dosing day and Day 2) and… Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Metabolic, Cardiovascular
What is being tested?
Tab carvedilol 25 mg, Tab carvedilol 6.25 mg and Powder carvedilol up to 2.5 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited Kingdom
Study dates
15 Jan 2013to 17 Jun 2013
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 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and ECG monitoring.
  • Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent.
  • A female subject is eligible to participate if she is of non-childbearing potential Female subjects of child bearing potential must agree to use contraception from screening until the follow-up visit.
  • Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods.
  • Body weight >= 50 kilogram (kg) and BMI within the range 18.5 to 29.9 kilogram per meter square (kg/m^2) (inclusive).
  • Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Show all 25Show fewer
  • Average QT corrected using Bazett's formula (QTcB) or QT corrected using Fridericia's formula (QTcF) <450 milliseconds (msec).
  • Suitable for cannulation and with adequate venous access. Exclusion criteria
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • Resting heart rate of <50 beats per minute (bpm) at screening
  • Any of the following abnormalities on 12-lead electrocardiogram (ECG) during screening: conduction abnormalities denoted by any of the following- PR interval <120 msec or >200 msec; non-specific IVCD (intra-ventricular conduction delay) with QRS duration >=110 msec and where the morphology does NOT meet criteria for left (LBBB) or right bundle branch block (RBBB); incomplete RBBB as defined by QRS duration >=100 msec but <120 msec with RBBB pattern; complete RBBB and LBBB; evidence of second- or third- degree atrio ventricular (AV) block; pathological Q-waves (Q-wave wider than 0.04 sec or depth not greater than 0.4-0.5 millivolt [mV]); evidence of ventricular pre-excitation; evidence of left axis deviation (left axis deviation is -30 to -90 degrees) but not normal leftward axis, ST-T wave abnormalities.
  • Documented history of low blood pressure (average systolic blood pressure [SBP] <= 110 millimeters of mercury [mm Hg] and/or DBP <=60 mm Hg) or semi-supine blood pressure below these values at time of screening.
  • Orthostatic hypotension diagnosed at screening (orthostatic hypotension will be defined as a reduction in systolic blood pressure of 20 mm Hg or more and/or a reduction in diastolic blood pressure of 10 mmHg or more within three minutes of standing upright from supine at screening).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • A positive pre-study drug/alcohol screen.
  • History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Unable to adhere with restrictions detailed in the informed consent or protocol.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Pregnant females as determined by positive serum or urine human chorionic gonadotropin (hCG) test at screening or prior to dosing.
  • Subject is a smoker, based on at least 12 months non-smoking history.
  • Lactating females.
  • Subjects who have asthma or a history of asthma or of bronchospasm. Subjects with a history of childhood asthma but are now asymptomatic may be included at the investigators discretion.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • GSK Investigational Site

    Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: A Four Way Crossover Study in Healthy Volunteers to Evaluate the Application of Stable Isotope Approach to Reduce Number of Subjects Needed for PK Studies

This will be a randomized, open-label, single dose, 4-period, period balanced, crossover study. There will be at least 5 days between dosing in each session. The study consists of Screening period (30 days prior to Day 1), Treatment period consisting of 4 dosing periods (Day 1 is the dosing day and Day 2) and Follow-up period (7-14 days post-last dose).

The detailed treatment regimen will be A and B (27.5 mg total maximum dose): Single oral dose of carvedilol 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol powder under fasted conditions; C (33.75 mg total maximum dose): Single oral dose of carvedilol 31.25 mg as 25 mg immediate release tablet, a 6.25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol powder under fasted conditions; D (27.5 mg total maximum dose): Single oral dose of carvedilol 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol powder under fed conditions. Approximately 15 subjects will be randomized to receive one of four treatment sequences (ADBC, BACD, CBDA, or DCAB).

The pharmacokinetic sampling and safety data will be collected in the Treatment period (Day 1 and 2).

Being tested
Tab carvedilol 25 mg, Tab carvedilol 6.25 mg, Powder carvedilol up to 2.5 mg
Keywords
pharmacokinetic, carvedilol, Stable isotope technique

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tab carvedilol 25 mgDrug

    Carvedilol 25 mg immediate release tablet

  • Tab carvedilol 6.25 mgDrug

    Carvedilol 6.25 mg immediate release tablet

  • Powder carvedilol up to 2.5 mgDrug

    Carvedilol up to 2.5 mg isotopically enriched drug substance powder

Study groups in NCT01793870
Study groupRoleWhat they receive
Treatment A (27.5 mg total maximum dose)ExperimentalSingle oral dose of carvedilol (25 milligram [mg]) as a 1 x 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Receives: Drug: Tab carvedilol 25 mg; Drug: Powder carvedilol up to 2.5 mg
Treatment B (27.5 mg total maximum dose)ExperimentalSingle oral dose of carvedilol (25 mg) as a 1 x 25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Receives: Drug: Tab carvedilol 25 mg; Drug: Powder carvedilol up to 2.5 mg
Treatment C (33.75 mg total maximum dose)ExperimentalSingle oral dose of carvedilol (31.25 mg) as a 1 x 25 mg immediate release tablet, a 1 x 6.25 mg immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fasted conditions.
Receives: Drug: Tab carvedilol 25 mg; Drug: Tab carvedilol 6.25 mg; Drug: Powder carvedilol up to 2.5 mg
Treatment D (27.5 mg total maximum dose)ExperimentalSingle oral dose of carvedilol (25 mg) as a 1 x 25 mg x immediate release tablet and up to 2.5 mg of enriched carvedilol drug substance under fed conditions.
Receives: Drug: Tab carvedilol 25 mg; Drug: Powder carvedilol up to 2.5 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The AUC for both the enriched and non-enriched R- and S-isomers of carvedilol

    The pharmacokinetic parameters will include area under the time concentration curve (AUC) for both the enriched and non-enriched R- and S-isomers of carvedilol

    Measured: Day 1:pre-dose, 15 minutes (mins), 30 mins, 45 mins, 1 hour (h), 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day 2: at 24 h and 36 h post dose

  2. The Cmax for both the enriched and non-enriched R- and S-isomers of carvedilol

    The pharmacokinetic parameters will include maximum drug concentration (Cmax) for both the enriched and non-enriched R- and S-isomers of carvedilol

    Measured: Day 1:pre-dose, 15 minutes (mins), 30 mins, 45 mins, 1 hour (h), 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day 2: at 24 h and 36 h post dose

Secondary outcomes (2)

  1. The Tmax for both the enriched and non-enriched R- and S-isomers of carvedilol (as data permit)

    The pharmacokinetic parameter will include the time when maximum drug concentration is reached (Tmax) for both the enriched and non-enriched R- and S-isomers of carvedilol

    Measured: Day 1:pre-dose, 15 minutes (mins), 30 mins, 45 mins, 1 hour (h), 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day 2: at 24 h and 36 h post dose

  2. The T1/2 for both the enriched and non-enriched R- and S-isomers of carvedilol (as data permit)

    The pharmacokinetic parameter will include the half life of the drug (T1/2) for both the enriched and non-enriched R- and S-isomers of carvedilol

    Measured: Day 1:pre-dose, 15 minutes (mins), 30 mins, 45 mins, 1 hour (h), 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day 2: at 24 h and 36 h post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2013 (estimated)
  2. Study start15 Jan 2013
  3. Primary completion17 Jun 2013
  4. Study completion17 Jun 2013

Resources

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
Other
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01793870
Sponsor's protocol ID
117058
Status last verified
Jun 2017
First submitted
14 Feb 2013
Last updated
12 Jun 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tab carvedilol 25 mg, Tab carvedilol 6.25 mg and Powder carvedilol up to 2.5 mg in people with Metabolic, Cardiovascular, run by GlaxoSmithKline at 1 site in United Kingdom.

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 25 inclusion and 0 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 12 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

The AUC for both the enriched and non-enriched R- and S-isomers of carvedilol (time frame: Day 1:pre-dose, 15 minutes (mins), 30 mins, 45 mins, 1 hour (h), 2 h, 3 h, 4 h, 6 h, 8 h and 12 h post-dose; Day 2: at 24 h and 36 h post dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01793870.

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 12 Jun 2017.

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