HealthyPhase 1NCT02661594
Thorough QT Study of Intravenous Amisulpride
A Phase 1 study testing APD421 5 mg, APD421 40 mg and Moxifloxacin in people with Healthy, run by Acacia Pharma Ltd.
Trial summary
Randomised, single-dose, crossover, placebo-controlled study to see if intravenous amisulpride has any effect on the heart rhythm, in particular the QT interval, in healthy adult volunteers. Read more about this study
- Who is it for?
- Ages 20 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- APD421 5 mg, APD421 40 mg and Moxifloxacin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Nov 2013to Mar 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female subjects aged between 20 and 45 years (inclusive) at screening.
- Signed informed consent in the local language prior to any study-mandated procedure.
- Japanese subjects defined as a person carrying a Japanese passport, who is a descendant of four Japanese grandparents and has not been outside Japan for more than five years prior to screening.
- The Caucasian subjects should be distinguished especially by very light to brown skin pigmentation and straight to wavy or curly hair, and should be indigenous to Europe, northern Africa, western Asia, and India. Therefore, the study may as well include Caucasian subjects from North America, Australia and South Africa
- No clinically significant findings on the physical examination at screening and at admission on Day -2.
- Body mass index (BMI) between 18 and 25 kg/m2 (inclusive) at screening and at admission on Day -2, body weight at least 48 kg.
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- Systolic blood pressure (SBP) 90-145 mmHg, diastolic blood pressure (DBP) 40-90 mmHg, and heart rate (HR) 40-90 bpm (all inclusive), measured on the left arm, after 10 minutes in the supine position at screening and at admission on Day -2.
- Triplicate 12-lead ECG without clinically relevant abnormalities measured after ten minutes in the supine position at screening and on admission on Day -2.
- 24-hour 12-lead Holter ECG or an equivalent assessment and/or submaximal exercise test without clinically relevant abnormalities measured at screening.
- Haematology, biochemistry and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening and at admission.
- Subjects must agree to use acceptable methods of contraception:
- Male subjects
- Male subjects must use medically acceptable methods of contraception if their female partner(s) is (are) pregnant or lactating from the time of the first administration of treatment or study medication until three months following administration of the last treatment or dose of study medication. Acceptable methods include:
- Condom used with spermicidal foam/gel/film/cream/suppository
- If the subject has undergone surgical sterilisation (vasectomy with documentation of azoospermia) a condom with spermicidal foam/gel/film/cream/suppository must be used.
- Use acceptable methods of contraception if the male subject's partner could become pregnant from the time of the first administration of treatment or study medication until three months following administration of the last treatment or dose of study medication. The acceptable methods of contraception are as follows:
- Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- Surgical sterilisation (vasectomy with documentation of azoospermia) and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository).
- The female partner uses oral contraceptives (combination oestrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository).
- The female partner uses medically prescribed topically-applied transdermal contraceptive patch and a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository).
- The female partner has undergone documented tubal ligation (female sterilisation). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository) must be used.
- The female partner has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS) and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository).
- True abstinence: When this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Female subjects
- Female subjects of childbearing potential must use medically acceptable methods of contraception from the time of the first administration of treatment or study medication until three months following administration of the last treatment or dose of study medication. Acceptable methods include:
- A documented placement of an IUD or IUS and the use of a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps) used with spermicidal foam/gel/film/cream/suppository]).
- Documented tubal ligation (female sterilisation). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository) should also be used.
- Double barrier method: Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- True abstinence: When this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) are not acceptable methods of contraception.
- Ability to communicate well with the Investigator in the local language, and to understand and comply with the requirements of the study.
Who cannot join
- Women who are pregnant and/or breastfeeding.
- Received amisulpride for any indication within the last 2 weeks.
- Allergy to amisulpride or any of the excipients of APD421.
- History of vestibular disorder or history of dizziness.
- Received anti-emetic therapy including corticosteroids within the last 2 weeks.
- History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug (appendectomy and herniotomy allowed, cholecystectomy not allowed).
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- History of epilepsy.
- History of clinically significant syncope.
- Family history of sudden death.
- Family history of premature cardiovascular death.
- Clinically significant history or family history of congenital long QT syndrome (e.g. Romano-Ward syndrome, Jervell and Lange-Nielson syndrome) or Brugada's syndrome.
- History of clinically significant arrhythmias and ischemic heart disease (especially ventricular arrhythmias, atrial fibrillation (AF), recent conversion from AF or coronary spasm).
- Conditions predisposing the volunteer to electrolyte imbalances (e.g. altered nutritional states, chronic vomiting, anorexia nervosa, bulimia nervosa).
- ECG abnormalities in the standard 12-lead ECG (at screening and Day -2) and 24-hour 12-lead Holter ECG or an equivalent assessment and/or submaximal exercise test (at screening) which in the opinion of the Investigator will interfere with the ECG analysis.
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This includes subjects with any of the following (at screening and Day -2 of Period 1):
- Sinus node dysfunction.
- Clinically significant PR (PQ) interval prolongation.
- Intermittent second or third degree atrioventricular (AV) block.
- Incomplete or complete bundle branch block.
- Abnormal T-wave morphology.
- Prolonged QT interval corrected with Bazett's formula (QTcB) >450 ms or shortened QTcB < 350 ms or family history of long QT syndrome.
- Subject with borderline deviations from these criteria may be included if the deviations do not pose a safety risk, and if agreed between the appointed Cardiologist and the PI.
- Signs and/or symptoms of a clinically relevant acute illness in the four-week period prior to screening.
- Veins unsuitable for intravenous puncture or cannulation on either arm (e.g. veins that are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture).
- Known hypersensitivity to any medicines administered in the trial.
- Treatment with any prescribed medication during the two weeks prior to first baseline day.
- Treatment with any over-the-counter (OTC) medications during the two weeks prior to first baseline day.
- Treatment with vitamins and/or minerals within 48 hours prior to the first baseline day.
- Treatment with another investigational drug within four weeks prior to dosing or having participated in more than three investigational drug studies within one year prior to dosing.
- Confirmed positive results from urine drug screen (amphetamines, benzodiazepines, cocaine, cannabinoids, opiates, barbiturates and methadone) or from the alcohol breath test at screening and on Day -2.
- History or clinical evidence of alcoholism or drug abuse. Alcohol abuse is defined as regular weekly intake of more than 14 units (Using alcohol tracker http://www.nhs.uk/Tools/Pages/NHSAlcoholtracker.aspx); drug abuse is defined as compulsive, repetitive and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms.
- Excessive caffeine consumption, defined as ≥800 mg per day at screening (800 mg = 7 cups of coffee or 16 cups of tea).
- Smoking within three months prior to screening or during the screening period.
- Loss of 250 mL or more blood within three months prior to screening.
- Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
- Positive results from the HIV serology at screening.
- Any circumstances or conditions, which, in the opinion of the Investigator, may affect full participation in the study or compliance with the protocol.
- Legal incapacity or limited legal capacity at screening.
About this study
Official title: A Randomised, Double-blind, Four-period Crossover Study to Investigate the Effect of Intravenous APD421 on Cardiac Conduction as Compared to Placebo and Moxifloxacin in Healthy Adult Subjects
Randomised, single-dose, crossover, placebo-controlled study to see if intravenous amisulpride has any effect on the heart rhythm, in particular the QT interval, in healthy adult volunteers.
Read the detailed description
Phase 1, randomised, single-dose, period-balanced, crossover, placebo- controlled study to assess the effects of iv doses of amisulpride on the QT interval, corrected for heart rate by Fridericia's formula (QTcF), in healthy male and female subjects of Caucasian and Japanese ethnicity aged 20-45 years.
- Conditions
- Healthy
- Being tested
- APD421 5 mg, APD421 40 mg, Moxifloxacin, Placebo
- Keywords
- TQT, amisulpride, volunteer, ECG
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APD421 5 mgDrug
Also called Amisulpride 5mg
Therapeutic dose of amisulpride
APD421 40 mgDrug
Also called Amisulpride 40mg
Supra-therapeutic dose of amisulpride
MoxifloxacinDrug
Positive control for assay sensitivity
PlaceboDrug
Placebo comparator to establish baseline for calculating change in QTcF
| Study group | Role | What they receive |
|---|---|---|
| ABCD | Experimental | A: APD421 5 mg followed by B: APD421 40 mg; C: Moxifloxacin 400 mg; D: Placebo. Receives: Drug: APD421 5 mg; Drug: APD421 40 mg; Drug: Moxifloxacin; Drug: Placebo |
| BDAC | Experimental | B: APD421 40 mg; D: Placebo. A: APD421 5 mg C: Moxifloxacin 400 mg; Receives: Drug: APD421 5 mg; Drug: APD421 40 mg; Drug: Moxifloxacin; Drug: Placebo |
| CADB | Experimental | C: Moxifloxacin 400 mg A: APD421 5 mg D: Placebo B: APD421 40 mg Receives: Drug: APD421 5 mg; Drug: APD421 40 mg; Drug: Moxifloxacin; Drug: Placebo |
| DCBA | Active comparator | D: Placebo C: Moxifloxacin 400 mg B: APD421 40 mg A: APD421 5 mg Receives: Drug: APD421 5 mg; Drug: APD421 40 mg; Drug: Moxifloxacin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal Mean ΔΔQTcF
Maximal mean placebo-corrected change from baseline of QTcF (QT interval corrected for heart rate using the Fridericia formula) for single 5 mg and 40 mg iv doses of APD421. At each time point (2 mins, 8 mins, etc) the QTcF is compared to the pre-dosing "baseline" value, in order to calculate the change in QTcF (ΔQTcF). The value of ΔQTcF at each time point is then compared against the same time point for a placebo infusion, and the difference is calculated (ΔΔQTcF).
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2016 (estimated)
- Study startNov 2013
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acacia Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gabriel Fox, MB BChir, Study director, Acacia Pharma Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02661594
- Sponsor's protocol ID
- DP10013
- Status last verified
- Nov 2018
- First submitted
- 14 Jan 2016
- Last updated
- 29 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Four-period Crossover Study to Investigate the Effect of Intravenous APD421 on Cardiac Conduction as Compared to Placebo and Moxifloxacin in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT02661594
- Acronym / sponsor ID
- DP10013
- Conditions
- Healthy
- Keywords
- TQT, amisulpride, volunteer, ECG
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Acacia Pharma LtdIndustry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 22 Jan 2016 (estimated)
- Results
- Posted 30 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomised, single-dose, crossover, placebo-controlled study to see if intravenous amisulpride has any effect on the heart rhythm, in particular the QT interval, in healthy adult volunteers.
Detailed description
Phase 1, randomised, single-dose, period-balanced, crossover, placebo- controlled study to assess the effects of iv doses of amisulpride on the QT interval, corrected for heart rate by Fridericia's formula (QTcF), in healthy male and female subjects of Caucasian and Japanese ethnicity aged 20-45 years.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ABCD | Experimental | Drug: APD421 5 mg, Drug: APD421 40 mg, Drug: Moxifloxacin, Drug: PlaceboA: APD421 5 mg followed by B: APD421 40 mg; C: Moxifloxacin 400 mg; D: Placebo. |
| BDAC | Experimental | Drug: APD421 5 mg, Drug: APD421 40 mg, Drug: Moxifloxacin, Drug: PlaceboB: APD421 40 mg; D: Placebo. A: APD421 5 mg C: Moxifloxacin 400 mg; |
| CADB | Experimental | Drug: APD421 5 mg, Drug: APD421 40 mg, Drug: Moxifloxacin, Drug: PlaceboC: Moxifloxacin 400 mg A: APD421 5 mg D: Placebo B: APD421 40 mg |
| DCBA | Active comparator | Drug: APD421 5 mg, Drug: APD421 40 mg, Drug: Moxifloxacin, Drug: PlaceboD: Placebo C: Moxifloxacin 400 mg B: APD421 40 mg A: APD421 5 mg |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (30 listed)
- Healthy male or female subjects aged between 20 and 45 years (inclusive) at screening.
- Signed informed consent in the local language prior to any study-mandated procedure.
- Japanese subjects defined as a person carrying a Japanese passport, who is a descendant of four Japanese grandparents and has not been outside Japan for more than five years prior to screening.
- The Caucasian subjects should be distinguished especially by very light to brown skin pigmentation and straight to wavy or curly hair, and should be indigenous to Europe, northern Africa, western Asia, and India. Therefore, the study may as well include Caucasian subjects from North America, Australia and South Africa
- No clinically significant findings on the physical examination at screening and at admission on Day -2.
Key exclusion criteria (38 listed)
- Women who are pregnant and/or breastfeeding.
- Received amisulpride for any indication within the last 2 weeks.
- Allergy to amisulpride or any of the excipients of APD421.
- History of vestibular disorder or history of dizziness.
- Received anti-emetic therapy including corticosteroids within the last 2 weeks.
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 |
|---|---|---|
| APD421 5 mgAlso: Amisulpride 5mgTherapeutic dose of amisulpride | Drug | ABCD, BDAC, CADB, DCBA |
| APD421 40 mgAlso: Amisulpride 40mgSupra-therapeutic dose of amisulpride | Drug | ABCD, BDAC, CADB, DCBA |
| MoxifloxacinPositive control for assay sensitivity | Drug | ABCD, BDAC, CADB, DCBA |
| PlaceboPlacebo comparator to establish baseline for calculating change in QTcF | Drug | ABCD, BDAC, CADB, DCBA |
Primary outcome
Maximal Mean ΔΔQTcF
Time frame: 24 hours
Maximal mean placebo-corrected change from baseline of QTcF (QT interval corrected for heart rate using the Fridericia formula) for single 5 mg and 40 mg iv doses of APD421. At each time point (2 mins, 8 mins, etc) the QTcF is compared to the pre-dosing "baseline" value, in order to calculate the change in QTcF (ΔQTcF). The value of ΔQTcF at each time point is then compared against the same time point for a placebo infusion, and the difference is calculated (ΔΔQTcF).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Gabriel Fox, MB BChir study director
Acacia Pharma Ltd
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing APD421 5 mg, APD421 40 mg and Moxifloxacin in people with Healthy, run by Acacia Pharma Ltd.
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 30 inclusion and 38 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 29 Nov 2018. 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?
Yes. Results are posted in the registry (first posted 30 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximal Mean ΔΔQTcF (time frame: 24 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 29 Nov 2018.