HealthyPhase 1NCT01692834
A Study to Compare the Bioavailability and Pharmacokinetics of Cyclosporine After Intravenous Administration of NEUROSTAT®, a CREMOPHOR® EL-free Lipid Emulsion, and SANDIMMUNE® Injection (a Suspension of Cyclosporine in CREMOPHOR® EL) in Healthy Volunteers
A Phase 1 study testing Sandimmune® Injection and NeuroSTAT® in people with Healthy, run by NeuroVive Pharmaceutical AB at 1 site in South Africa.
Trial summary
To compare the bioavailability, pharmacokinetic profiles and the tolerability of two formulations of intravenous cyclosporine in healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Sandimmune® Injection and NeuroSTAT®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteSouth Africa
- Study dates
- Jun 2009to Jan 2010
- 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 male and female subjects 18 to < 56 years of age.
- Caucasian and Non-Caucasian subjects.
- Body mass within 15% of the ideal mass in relation to height and age (this relates to a Body Mass Index [BMI] of 19 - 33 kg/m2).
- Body mass not less than 60 kg and not more than 100 kg.
- Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results within the laboratory reference ranges for the relevant laboratory tests (unless the investigator considered the deviation to be irrelevant for the purpose of the study).
- Normal 12-lead ECG and vital signs, or abnormalities which the investigator did not consider a disqualification for participation in the study.
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- Willingness to undergo pre-, interim- and post-study physical examinations, vital signs and laboratory investigations.
- Ability to comprehend and willingness to have signed both statements of informed consent (for screening and period-related procedures).
- Non-smoker or past smoker who had stopped the use of any form of tobacco, including snuff or similar products, at least 3 months before the first administration of study medication.
- Female subjects of childbearing potential, but who were not pregnant, not lactating and who were either abstaining from sexual activity or using medically acceptable and reliable methods of contraception for the duration of the study. Examples of reliable methods of contraception included tubal ligation, hysterectomy, intrauterine device, or a barrier method combined with a spermicide. The use of hormonal contraceptives (including a hormonal intrauterine device) was not allowed. Females not of childbearing potential may have been included if they had no menstrual period for one year and were considered as post-menopausal. A pregnancy test was performed prior to each cyclosporine dosing to all women of childbearing potential.
Who cannot join
- Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to have limited the validity of consent to participate in the study or limited the ability to comply with protocol requirements.
- History of, or current compulsive alcohol abuse (> 10 drinks weekly), or regular exposure to other substances of abuse.
- Use of any medication, prescribed or over-the-counter, within 2 weeks prior to the first administration of study medication (within 2 weeks prior to dosing in Treatment period 2 for Cohort 2) except if this would not have affected the outcome of the study in the opinion of the investigator.
- Females taking oral or transdermal hormonal contraceptives within 14 days preceding dosing or having used implanted or injected hormonal contraceptives within 6 months prior to dosing.
- Participation in another study with an experimental drug, where the last administration (of previous study medication) was within 12 weeks before the first administration of study medication.
- Treatment within the previous 3 months with any drug with a well-defined potential for adversely affecting a major organ or system.
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- A major illness during the 3 months before commencement of the screening period.
- History of hypersensitivity to the study medication, carrier substances, or any related medication.
- History of any type of malignancy.
- Tendency toward recurrent infections, known untreated parasitic infection, or history of primary or secondary immunodeficiency.
- History of allergy to soybeans or soy products.
- History of allergy to eggs or egg products.
- History of bronchial asthma or any other bronchospastic diseases.
- History of epilepsy.
- History of porphyria.
- History of psoriasis.
- History of atopic dermatitis.
- History of elevated cholesterol levels of above 6.5 mmol/L.
- History of gout.
- History of rheumatoid arthritis.
- History or evidence of kidney disease or renal failure.
- Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to have influenced study outcome.
- Total bilirubin concentration, which exceeds 10% of normal laboratory ranges (4-30 μmol/L).
- Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the first administration of study medication.
- Diagnosis of hypotension made during the screening period.
- Diagnosis of hypertension made during the screening period or current diagnosis of hypertension.
- Resting pulse rate of > 100 beats per minute or < 40 beats per minute during the screening period, either supine or standing.
- Positive testing for HIV and Hepatitis B and/or Hepatitis C.
- Positive urine screen for drugs of abuse.
- Positive urine screen for tobacco use.
- A serum pregnancy test for females (beta human chorionic gonadotropin [β-HCG]) either positive or not performed or lactation.
- Vaccination with any vaccine (including live, attenuated virus or bacterial vaccines) within 4 weeks of first dose or planning to have had a vaccination within 3 months after the second dose.
- Subjects with close family members (spouse/partner/children) receiving a live vaccine during the study, or within 3 months after the second dose.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Study to Compare the Bioavailability and Pharmacokinetics of Cyclosporine After Intravenous Administration of NEUROSTAT®, a CREMOPHOR® EL-free Lipid Emulsion, and SANDIMMUNE® Injection (a Suspension of Cyclosporine in CREMOPHOR® EL) in Healthy Volunteers ; An Open-label, Subject-blind, Laboratory-blind, Single-dose (5 mg/kg Infusion), Randomised, Two-period Crossover Tolerability Study Carried Out in Healthy Male and Female Subjects
To compare the bioavailability, pharmacokinetic profiles and the tolerability of two formulations of intravenous cyclosporine in healthy volunteers.
Read the detailed description
Participants were randomized into two treatment sequences: the test product followed by the reference product or vice versa. There was a washout period set to 14-21 days between the first and second treatment period. Through an indwelling IV cannula, the subjects received either 5 mg/kg NeuroSTAT® (test) or 5 mg/kg Sandimmune® (reference), infused at a constant rate over 4 h with a syringe pump. A total of 22 blood samples for Cyclosporine analysis were obtained pre-dose and at pre specified time points with last sample 48 h after start of infusion.
- Conditions
- Healthy
- Being tested
- Sandimmune® Injection, NeuroSTAT®
- Keywords
- bioequivalence, pharmacokinetics, tolerability, safety, ciclosporin, cyclosporine, cyclosporine A, Sandimmune, Sandimmun, CicloMulsion, NeuroSTAT
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sandimmune® InjectionDrug
NeuroSTAT®Drug
Also called CicloMulsion® (ready-to-use lipid emulsion of Cyclosporine A)
| Study group | Role | What they receive |
|---|---|---|
| Cyclosporine in Cremophor EL® | Active comparator | Dosing 5 mg/kg infused at a constant rate over 4 h with a syringe pump. Receives: Drug: Sandimmune® Injection |
| Cyclosporine in lipid emulsion | Active comparator | Dosing 5 mg/kg infused at a constant rate over 4 h with a syringe pump. Receives: Drug: NeuroSTAT® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bioequivalence between test and reference product.
To compare the bioavailability and pharmacokinetics of a single dose of the test product, NeuroSTAT® 5 mg/mL ready-to-use Cremophor® EL-free cyclosporine with the reference product, Sandimmune® Injection 50 mg/mL Cremophor® EL suspension (each 1 mL diluted in 20 mL saline). For this purpose the pharmacokinetics of cyclosporine was compared during and after intravenous (IV) infusion, over 4 hours, of a single dose of 5 mg/kg of each of the two formulations to healthy subjects. The primary parameters are area under the blood concentration-time curves (AUC) from time zero to time of last measurable concentration (AUC0-last), time zero to infinity (AUC0-∞), time 4 h to infinity (AUC4-∞). Point estimates and 90 % Confidence IntervaI (CI) for the NeuroSTAT®/Sandimmune® geometric mean ratios of all variables are calculated. The two products are considered bioequivalent if the 90 % CI for the primary variables are within the FDA and EMA approved range of 0.8 and 1.25.
Measured: Repeated samplings from pre-dose to 48 hours
Secondary outcomes (1)
Tolerability comparison of test and reference product
To compare the tolerability profiles of the test product, NeuroSTAT® 5 mg/mL ready-to-use Cremophor® EL-free cyclosporine USP/Ph. Eur. lipid emulsion, with the reference product, Sandimmune® Injection (cyclosporine injection, USP) 50 mg/mL Cremophor® EL suspension (each 1 mL diluted in 20 mL saline). The proportions of overall adverse events and adverse events per organ class (as defined by the Medical Dictionary for Regulatory Activities) are compared between NeuroSTAT® and Sandimmune® by means of 95 % CI for the difference between paired proportions and p-values.
Measured: From start of study drug administration to last blood sampling at 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2012 (estimated)
- Study startJun 2009
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- NeuroVive Pharmaceutical AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eduard FW Krantz, Dr, Principal investigator, Parexel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01692834
- Sponsor's protocol ID
- 99752
- Status last verified
- Jul 2014
- First submitted
- 11 Sep 2012
- Last updated
- 1 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Compare the Bioavailability and Pharmacokinetics of Cyclosporine After Intravenous Administration of NEUROSTAT®, a CREMOPHOR® EL-free Lipid Emulsion, and SANDIMMUNE® Injection (a Suspension of Cyclosporine in CREMOPHOR® EL) in Healthy Volunteers ; An Open-label, Subject-blind, Laboratory-blind, Single-dose (5 mg/kg Infusion), Randomised, Two-period Crossover Tolerability Study Carried Out in Healthy Male and Female Subjects
- ClinicalTrials.gov ID
- NCT01692834
- Acronym / sponsor ID
- 99752
- Conditions
- Healthy
- Keywords
- bioequivalence, pharmacokinetics, tolerability, safety, ciclosporin, cyclosporine, cyclosporine A, Sandimmune
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- NeuroVive Pharmaceutical ABIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 25 Sep 2012 (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.
To compare the bioavailability, pharmacokinetic profiles and the tolerability of two formulations of intravenous cyclosporine in healthy volunteers.
Detailed description
Participants were randomized into two treatment sequences: the test product followed by the reference product or vice versa. There was a washout period set to 14-21 days between the first and second treatment period. Through an indwelling IV cannula, the subjects received either 5 mg/kg NeuroSTAT® (test) or 5 mg/kg Sandimmune® (reference), infused at a constant rate over 4 h with a syringe pump. A total of 22 blood samples for Cyclosporine analysis were obtained pre-dose and at pre specified time points with last sample 48 h after start of infusion.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclosporine in Cremophor EL® | Active comparator | Drug: Sandimmune® InjectionDosing 5 mg/kg infused at a constant rate over 4 h with a syringe pump. |
| Cyclosporine in lipid emulsion | Active comparator | Drug: NeuroSTAT®Dosing 5 mg/kg infused at a constant rate over 4 h with a syringe pump. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Healthy male and female subjects 18 to < 56 years of age.
- Caucasian and Non-Caucasian subjects.
- Body mass within 15% of the ideal mass in relation to height and age (this relates to a Body Mass Index [BMI] of 19 - 33 kg/m2).
- Body mass not less than 60 kg and not more than 100 kg.
- Findings within the range of clinical acceptability in medical history and physical examination, and laboratory results within the laboratory reference ranges for the relevant laboratory tests (unless the investigator considered the deviation to be irrelevant for the purpose of the study).
Key exclusion criteria (33 listed)
- Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to have limited the validity of consent to participate in the study or limited the ability to comply with protocol requirements.
- History of, or current compulsive alcohol abuse (> 10 drinks weekly), or regular exposure to other substances of abuse.
- Use of any medication, prescribed or over-the-counter, within 2 weeks prior to the first administration of study medication (within 2 weeks prior to dosing in Treatment period 2 for Cohort 2) except if this would not have affected the outcome of the study in the opinion of the investigator.
- Females taking oral or transdermal hormonal contraceptives within 14 days preceding dosing or having used implanted or injected hormonal contraceptives within 6 months prior to dosing.
- Participation in another study with an experimental drug, where the last administration (of previous study medication) was within 12 weeks before the first administration of study medication.
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 |
|---|---|---|
| Sandimmune® Injection | Drug | Cyclosporine in Cremophor EL® |
| NeuroSTAT®Also: CicloMulsion® (ready-to-use lipid emulsion of Cyclosporine A) | Drug | Cyclosporine in lipid emulsion |
Primary outcome
Bioequivalence between test and reference product.
Time frame: Repeated samplings from pre-dose to 48 hours
To compare the bioavailability and pharmacokinetics of a single dose of the test product, NeuroSTAT® 5 mg/mL ready-to-use Cremophor® EL-free cyclosporine with the reference product, Sandimmune® Injection 50 mg/mL Cremophor® EL suspension (each 1 mL diluted in 20 mL saline). For this purpose the pharmacokinetics of cyclosporine was compared during and after intravenous (IV) infusion, over 4 hours, of a single dose of 5 mg/kg of each of the two formulations to healthy subjects. The primary parameters are area under the blood concentration-time curves (AUC) from time zero to time of last measurable concentration (AUC0-last), time zero to infinity (AUC0-∞), time 4 h to infinity (AUC4-∞). Point estimates and 90 % Confidence IntervaI (CI) for the NeuroSTAT®/Sandimmune® geometric mean ratios of all variables are calculated. The two products are considered bioequivalent if the 90 % CI for the primary variables are within the FDA and EMA approved range of 0.8 and 1.25.
1 secondary outcome
Tolerability comparison of test and reference product
Time frame: From start of study drug administration to last blood sampling at 48 hours
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 1 Aug 2014.
- Ehinger KH, Hansson MJ, Sjövall F, Elmér E. Bioequivalence and tolerabilityLink provided by the sponsor.
- Errata to publicationLink provided by the sponsor.
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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.
Eduard FW Krantz, Dr principal investigator
Parexel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sandimmune® Injection and NeuroSTAT® in people with Healthy, run by NeuroVive Pharmaceutical AB at 1 site in South Africa.
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 10 inclusion and 33 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 1 Aug 2014. 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 South Africa. 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?
Bioequivalence between test and reference product. (time frame: Repeated samplings from pre-dose to 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 1 Aug 2014; AzTrials last refreshed its copy on 8 Nov 2026.