Dose Finding StudyPhase 1NCT03595189
Safety, Tolerability and Pharmacokinetic Profile of an Infusion of Cilastatin in Healthy Volunteers.
A Phase 1 study testing Cilastatin in people with Dose Finding Study, run by Spherium Biomed at 1 site in Spain.
Trial summary
This is a phase I, randomized, single-blind, parallel group, placebo-controlled, multi-cohort, first-in-human dose escalation study of a single IV 3-hour administration of Cilastatin as stand-alone in healthy male and female volunteers. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Dose Finding Study
- What is being tested?
- Cilastatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteSpain
- Study dates
- 19 Jun 2018to 9 Aug 2018
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female subjects, 18-45 years (inclusive) of age at the time of enrolment.
- Male and female subjects willing and able to give their written consent to participate in the trial after having received information about the study design, the objectives of the project, the possible derivative risks, and their right to withdraw from the study at any time and for any reason.
- Body weight within normal range (Quetelet's index between 19 and 30 expressed as kg/m2 and weigh at least 50 kg and no more than 100 kg inclusive).
- Normal clinical records and physical examination.
- Laboratory tests (hematology, biochemistry and urine analysis) within the range of normal values, per the Biochemistry laboratory reference values of the 'Hospital Universitario La Paz'. Variations may be admitted per the clinical criteria of the clinical investigator.
- Clinically acceptable temperature, blood pressure and pulse rate in supine and standing position (SBP between 100-140 mm Hg/ DBP between 50-90 mm Hg / HR between 50-100 bpm). Blood pressure and pulse will be measured after a minimum of 3 minutes of resting.
- To be able to understand the nature of the study and comply with all their requirements.
Who cannot join
- Women of childbearing potential who planned to become pregnant, were pregnant and/or breast-feeding, or did not wish to use an effective contraceptive method (hormonal contraceptives [implant, patches, oral]) or double-barrier methods [any double combination of: IUD, male or female prophylactics with spermicidal gel, diaphragm, contraceptive sponge, cervical cap]).
- History of alcohol dependence or drug abuse in the last 1 year or daily consumption of alcohol > 40 g/day for men or 24 g/day for women.
- Heavy consumer of stimulating beverages (>5 coffees, teas, chocolate or cola drinks per day).
- Background of allergy, idiosyncrasy or hypersensitivity to drugs.
- Intake of any medication within 4 days prior and during visit 2 or Xanthine containing foods or beverages or herbal remedies that could interfere with pharmacokinetics of the study drug, except allowed contraceptive medication for female subjects.
- Positive serology for hepatitis B, C or HIV.
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- Background or clinical evidence of cardiovascular, respiratory, renal, hepatic, endocrine, gastrointestinal, haematological or neurological disease or other chronic diseases.
- Twelve lead ECG obtained at screening with PR ≥ 220 msec, QRS ≥120 msec and QTc ≥ 440 msec, bradycardia (<50 bpm) or clinically significant minor ST wave changes or any other abnormal changes on the screening ECG that would interfere with measurement of the QT interval.
- Having undergone major surgery during the previous 6 months.
- Smokers (refrained from any tobacco usage, including smokeless tobacco, nicotine patches, etc.) from 6 months prior to drug administration.
- Participation in another clinical trial during the 3 months preceding the drug administration.
- Donation of blood during the 4 weeks preceding the drug administration.
- Acute illness within four weeks before drug administration.
- Clinically significant abnormal laboratory values (as determined by the PI) at the screening evaluation.
- Existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the drug, i.e. impaired renal or hepatic function, diabetes mellitus, cardiovascular abnormalities, chronic symptoms of pronounced constipation or diarrhoea or conditions associated with total or partial obstruction of the urinary tract
- Positive results of the drugs at screening period or at visit 2. A minimum list of 6 drugs will be screened for inclusion: Amphetamines, Cocaine, Ethanol, Opiates, Benzodiazepines and Cannabinoids (positive results may be repeated at the discretion of the investigator team).
Trial locations and contacts
1 site in 1 country.
Spain1 site
Clinical Trials Unit, School of Medicine, Universidad Autónoma de Madrid
Madrid, 28029
About this study
Official title: Dose Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of an Infusion of Cilastatin in Healthy Volunteers.
This is a phase I, randomized, single-blind, parallel group, placebo-controlled, multi-cohort, first-in-human dose escalation study of a single IV 3-hour administration of Cilastatin as stand-alone in healthy male and female volunteers.
The study objectives are:
The evaluation of safety and tolerability of single intravenous doses of cilastatin in healthy volunteers administered as a 3-hour infusion.
The evaluation of the pharmacokinetic characteristics of Cilastatin after a single 3-hour infusion dose.
Read the detailed description
The study is designed as a phase I, randomized, single-blind, parallel group, placebo-controlled, multi-cohort, first-in-human dose escalation study of a single IV 3-hour administration of Cilastatin as stand-alone in healthy male and female volunteers.
The study will involve 24 healthy male and female healthy subjects, divided in three study cohorts (8 subjects per cohort). The study is a dose escalating study, starting from 3 g of Cilastatin administered intravenously in 3 hours.
Eight subjects will be randomized and assigned to either the study drug or placebo group for each study cohort in a 3:1 ratio (6 actives and 2 placebos). Randomization will also be gender balanced within each study cohort. The planned dose escalation scheme should not occur before participants in the previous dose level have been treated and safety profile of Cilastatin from those participants are assessed in accordande with the protocol.
- Conditions
- Dose Finding Study
- Being tested
- Cilastatin, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CilastatinDrug
Also called Cilastatin sodium
Dose escalation 3-hour single intravenous administration
PlaceboDrug
3-hour single intravenous administration
| Study group | Role | What they receive |
|---|---|---|
| Cilastatin Dose 1 | Experimental | Starting dose (3g of Cilastatin) Single intravenous administration during 3 hours. Receives: Drug: Cilastatin |
| Cilastatin Dose 2 | Experimental | Dose escalation Single intravenous administration during 3 hours. Receives: Drug: Cilastatin |
| Cilastatin Dose 3 | Experimental | Dose escalation Single intravenous administration during 3 hours. Receives: Drug: Cilastatin |
| Placebo | Placebo comparator | Saline solution for infusion Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Measured: From baseline up to follow-up (approximately 7 days after treatment administration).
Safety measures: Changes in Heart rate values will be assessed for each dose level of cilastatin
Measured: From baseline up to follow-up (approximately 7 days after treatment administration).
Safety measures: Changes in Blood pressure values will be assessed for each dose level of cilastatin
Measured: From baseline up to follow-up (approximately 7 days after treatment administration).
Safety measures: Changes in Body temperature values will be assessed for each dose level of cilastatin
Measured: From baseline up to follow-up (approximately 7 days after treatment administration).
Safety measures: Changes in clinical Laboratory testing will be assessed for each dose level of cilastatin.
Measured: From baseline up to follow-up (approximately 7 days after treatment administration)
Safety measures: Changes in Electrocardiogram (ECG) parameters will be assessed for each dose level of cilastatin.
Changes in QTc Interval will be assessed.
Measured: From baseline up to follow-up (approximately 7 days after treatment administration).
Safety measures: Continuous cardiac monitoring (by a holter monitor) will be assessed for each dose level of cilastatin.
Changes in electrocardiography heart activity will be assessed.
Measured: From baseline up to 24 h Post-dose
Assessment of any infusion site reaction
Measured: From baseline up to follow-up (approximately 7 days after treatment administration).
Secondary outcomes (3)
Determination of the Area under the curve versus time
Measured: From baseline up to 24 hours post start of drug administration
Determination of plasma concentrations
Measured: From baseline up to 24 hours post start of drug administration
Determination of renal clearance
Measured: From baseline up to 24 hours post start of drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2018
- Study start19 Jun 2018
- Primary completion9 Aug 2018
- Study completion9 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Dose Finding StudyStudies 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
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spherium Biomed
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hospital Universitario La Paz
- Responsible party
- Sponsor
- Investigators
- Jesús Frías, MD, Principal investigator, Hospital Universitario La Paz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03595189
- Sponsor's protocol ID
- SP15016-09
- Other IDs
- 2017-004795-63, 2017
- Status last verified
- Oct 2018
- First submitted
- 18 Jun 2018
- Last updated
- 9 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Faubel S. Acute Cardiac Injury Mediates a Distinct Form of CKD: Is This Cardiorenal Syndrome Type 7? J Am Soc Nephrol. 2025 Dec 1;36(12):2317-2319. doi: 10.1681/ASN.0000000905. Epub 2025 Oct 27. No abstract available.
PubMed 41143893Funahashi Y, Hebert JF, Munhall A, Aomura D, Burfeind KG, Nguyen ED, Groat T, Nickerson MN, Eiwaz MB, Nelson JW, Andeen NK, Yanagita M, Gurley SB, Hutchens MP. Cardiac LIM Protein, Kidney Fibrosis, and Vascular Change after Acute Cardiorenal Syndrome. J Am Soc Nephrol. 2025 Dec 1;36(12):2330-2347. doi: 10.1681/ASN.0000000774. Epub 2025 Jun 19.
PubMed 40536823
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of an Infusion of Cilastatin in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT03595189
- Acronym / sponsor ID
- SP15016-09
- Conditions
- Dose Finding Study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Spherium BiomedIndustry (pharma, biotech, devices)
- Collaborators
- Hospital Universitario La Paz
- Study start
- 19 Jun 2018 (actual)
- Primary completion
- 9 Aug 2018 (actual)
- Study completion
- 9 Aug 2018 (actual)
- First posted
- 23 Jul 2018 (actual)
- 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.
This is a phase I, randomized, single-blind, parallel group, placebo-controlled, multi-cohort, first-in-human dose escalation study of a single IV 3-hour administration of Cilastatin as stand-alone in healthy male and female volunteers.
The study objectives are:
The evaluation of safety and tolerability of single intravenous doses of cilastatin in healthy volunteers administered as a 3-hour infusion.
The evaluation of the pharmacokinetic characteristics of Cilastatin after a single 3-hour infusion dose.
Detailed description
The study is designed as a phase I, randomized, single-blind, parallel group, placebo-controlled, multi-cohort, first-in-human dose escalation study of a single IV 3-hour administration of Cilastatin as stand-alone in healthy male and female volunteers.
The study will involve 24 healthy male and female healthy subjects, divided in three study cohorts (8 subjects per cohort). The study is a dose escalating study, starting from 3 g of Cilastatin administered intravenously in 3 hours.
Eight subjects will be randomized and assigned to either the study drug or placebo group for each study cohort in a 3:1 ratio (6 actives and 2 placebos). Randomization will also be gender balanced within each study cohort. The planned dose escalation scheme should not occur before participants in the previous dose level have been treated and safety profile of Cilastatin from those participants are assessed in accordande with the protocol.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cilastatin Dose 1 | Experimental | Drug: CilastatinStarting dose (3g of Cilastatin) Single intravenous administration during 3 hours. |
| Cilastatin Dose 2 | Experimental | Drug: CilastatinDose escalation Single intravenous administration during 3 hours. |
| Cilastatin Dose 3 | Experimental | Drug: CilastatinDose escalation Single intravenous administration during 3 hours. |
| Placebo | Placebo comparator | Drug: PlaceboSaline solution for infusion |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Healthy male or female subjects, 18-45 years (inclusive) of age at the time of enrolment.
- Male and female subjects willing and able to give their written consent to participate in the trial after having received information about the study design, the objectives of the project, the possible derivative risks, and their right to withdraw from the study at any time and for any reason.
- Body weight within normal range (Quetelet's index between 19 and 30 expressed as kg/m2 and weigh at least 50 kg and no more than 100 kg inclusive).
- Normal clinical records and physical examination.
- Laboratory tests (hematology, biochemistry and urine analysis) within the range of normal values, per the Biochemistry laboratory reference values of the 'Hospital Universitario La Paz'. Variations may be admitted per the clinical criteria of the clinical investigator.
Key exclusion criteria (16 listed)
- Women of childbearing potential who planned to become pregnant, were pregnant and/or breast-feeding, or did not wish to use an effective contraceptive method (hormonal contraceptives [implant, patches, oral]) or double-barrier methods [any double combination of: IUD, male or female prophylactics with spermicidal gel, diaphragm, contraceptive sponge, cervical cap]).
- History of alcohol dependence or drug abuse in the last 1 year or daily consumption of alcohol > 40 g/day for men or 24 g/day for women.
- Heavy consumer of stimulating beverages (>5 coffees, teas, chocolate or cola drinks per day).
- Background of allergy, idiosyncrasy or hypersensitivity to drugs.
- Intake of any medication within 4 days prior and during visit 2 or Xanthine containing foods or beverages or herbal remedies that could interfere with pharmacokinetics of the study drug, except allowed contraceptive medication for female subjects.
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 |
|---|---|---|
| CilastatinAlso: Cilastatin sodiumDose escalation 3-hour single intravenous administration | Drug | Cilastatin Dose 1, Cilastatin Dose 2, Cilastatin Dose 3 |
| Placebo3-hour single intravenous administration | Drug | Placebo |
Primary outcome
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Time frame: From baseline up to follow-up (approximately 7 days after treatment administration).
Safety measures: Changes in Heart rate values will be assessed for each dose level of cilastatin
Time frame: From baseline up to follow-up (approximately 7 days after treatment administration).
Safety measures: Changes in Blood pressure values will be assessed for each dose level of cilastatin
Time frame: From baseline up to follow-up (approximately 7 days after treatment administration).
Safety measures: Changes in Body temperature values will be assessed for each dose level of cilastatin
Time frame: From baseline up to follow-up (approximately 7 days after treatment administration).
Safety measures: Changes in clinical Laboratory testing will be assessed for each dose level of cilastatin.
Time frame: From baseline up to follow-up (approximately 7 days after treatment administration)
Safety measures: Changes in Electrocardiogram (ECG) parameters will be assessed for each dose level of cilastatin.
Time frame: From baseline up to follow-up (approximately 7 days after treatment administration).
Changes in QTc Interval will be assessed.
Safety measures: Continuous cardiac monitoring (by a holter monitor) will be assessed for each dose level of cilastatin.
Time frame: From baseline up to 24 h Post-dose
Changes in electrocardiography heart activity will be assessed.
Assessment of any infusion site reaction
Time frame: From baseline up to follow-up (approximately 7 days after treatment administration).
3 secondary outcomes
Determination of the Area under the curve versus time
Time frame: From baseline up to 24 hours post start of drug administration
Determination of plasma concentrations
Time frame: From baseline up to 24 hours post start of drug administration
Determination of renal clearance
Time frame: From baseline up to 24 hours post start of drug administration
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 9 Oct 2018.
- Derived from this study: PubMed 41143893Faubel S. Acute Cardiac Injury Mediates a Distinct Form of CKD: Is This Cardiorenal Syndrome Type 7? J Am Soc Nephrol. 2025 Dec 1;36(12):2317-2319. doi: 10.1681/ASN.0000000905. Epub 2025 Oct 27. No abstract available.
- Derived from this study: PubMed 40536823Funahashi Y, Hebert JF, Munhall A, Aomura D, Burfeind KG, Nguyen ED, Groat T, Nickerson MN, Eiwaz MB, Nelson JW, Andeen NK, Yanagita M, Gurley SB, Hutchens MP. Cardiac LIM Protein, Kidney Fibrosis, and Vascular Change after Acute Cardiorenal Syndrome. J Am Soc Nephrol. 2025 Dec 1;36(12):2330-2347. doi: 10.1681/ASN.0000000774. Epub 2025 Jun 19.
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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.
Jesús Frías, MD principal investigator
Hospital Universitario La Paz
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 Cilastatin in people with Dose Finding Study, run by Spherium Biomed at 1 site in Spain.
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 7 inclusion and 16 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 9 Oct 2018. 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 Spain. 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. Some participants in this study may receive a placebo. 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?
Number of subjects with adverse events (AEs) and serious adverse events (SAEs) (time frame: From baseline up to follow-up (approximately 7 days after treatment administration).). The study lists 8 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 NCT03595189, which also lists 2 linked publications.
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 9 Oct 2018.