Renal ImpairmentPhase 1NCT01504165
Pharmacokinetics in Subjects With Renal Impairment
A Phase 1 study testing cilengitide 2000mg, cilengitide 1000mg and cilengitide > 1000mg and up to 2000mg in people with Renal Impairment, run by Merck KGaA, Darmstadt, Germany at 2 sites in Germany.
Trial summary
This is an open-label, non-randomized, parallel-group, mono-center, single intravenous dose, Phase I trial to investigate the Pharmacokinetic (PK) and safety of cilengitide in subjects with different grades of renal impairment as compared to subjects with normal renal function. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Impairment
- What is being tested?
- cilengitide 2000mg, cilengitide 1000mg and cilengitide > 1000mg and up to 2000mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesGermany
- Study dates
- Jan 2012to Apr 2012
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index (BMI): ≥ 18 kg/m² and ≤ 35 kg/m²
- For subjects with normal renal function:
- Vital signs (pulse rate and blood pressure) within the normal range or showing no clinically relevant deviation
- Estimated creatinine clearance according to the MDRD equation of ≥ 90 mL/min at Screening
- For subjects with impaired renal function:
- Laboratory parameters should be within acceptable range for subjects with renal impairment,
- Vital signs: Pulse rate within the normal range of 45-100 beats/minute in supine position after 5 minutes of rest. Blood pressure diastolic below 100 mmHg, and systolic below 160 mmHg for Groups 1-3 and below 180 mmHg for Group 4a and 4b, in supine position after 5 minutes of rest
- Calculated creatinine clearance according to the MDRD equation of < 90 mL/min at Screening and the possibility of stratification to one of the Groups.
Who cannot join
- History of malignant disease within the last 5 years or acute malignant disease
- Medical history of wound healing problems and/or any current open wounds
- Current or history of bleeding disorders and/or history of thromboembolic events (considering family history as well); thrombolytics or oral or parenteral anticoagulants within 30 days prior to Day 1
- Electrocardiogram recording (12-lead ECG) with signs of clinically relevant pathology as judged by the Investigator
- For subjects with impaired renal function:
- Chronic heart failure non stabilized (New York Heart Association [NYHA] class III and IV)
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- Acute renal failure of any etiology (including viral, toxic, or drug induced)
- Requiring dialysis
- History of renal transplantation
- Uncontrolled diabetes mellitus as judged by the Investigator
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
For Research Sites contact Merck KGaA Communication Center in
Darmstadt
CRS Clincial Research Services Kiel GmbH
Kiel
About this study
Official title: A Phase I, Open-label, Parallel-group, Mono-center Trial to Investigate the Pharmacokinetics of a Single Intravenous Dose of Cilengitide in Subjects With Mild, Moderate or Severe Renal Impairment Compared to Subjects With Normal Renal Function
This is an open-label, non-randomized, parallel-group, mono-center, single intravenous dose, Phase I trial to investigate the Pharmacokinetic (PK) and safety of cilengitide in subjects with different grades of renal impairment as compared to subjects with normal renal function.
Read the detailed description
Subjects with impaired renal function will be screened and will be stratified by their estimated glomerular filtration rate (GFR) according to the Modification of Diet in Renal Disease (MDRD) equation and assigned to one of the stratification groups defined below:
Group Number/Renal function/Creatinine Clearance (GFR according to MDRD)
- Normal renal function (≥ 90 mL/min)
- Mild renal impairment (60 - 89 mL/min)
- Moderate renal impairment (30 - 59 mL/ min) 4a: Severe renal impairment (< 30 mL/min) - no dialysis required 4b: (if applicable) Severe renal impairment (< 30 mL/min) - no dialysis required
Subjects in Groups 2 and 3 will receive a single dose of 2000mg of cilengitide as 1-hour i.v. infusion. Subjects from group 4a will receive a single dose of 1000mg of cilengitide as 1-hour i.v. infusion . PK samples will be collected and basic PK parameters will be calculated. The safety, tolerability, and PK will be evaluated by the Safety Monitoring Committee (SMC). If the SMC has no concerns, Group 4b will be treated with a higher dose (up to 2000mg) of cilengitide. Then, Group 1 (healthy subjects) will be started after the last subject with renal impairment (in either Group 2, 3, or 4a; or in Group 4b, if applicable) has completed all activities on Day 3. They will also receive a single dose of 2000mg of cilengitide as 1-hour i.v. infusion.
The duration of the trial from the first subject enrolled to the last subject last visit will be approximately 6 months (approximately 8 months, in case Group 4b is included). Each subject will participate in the trial for up to 35 days, including screening and the end of trial examination.
- Conditions
- Renal Impairment
- Being tested
- cilengitide 2000mg, cilengitide 1000mg, cilengitide > 1000mg and up to 2000mg
- Keywords
- Renal impairment, Pharmacokinetic, cilengitide, subjects with mild, moderate or severe renal impairment compared to subjects with normal renal function
- Medical subject headings
- Renal Insufficiency, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cilengitide 2000mgDrug
A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1
cilengitide 2000mgDrug
A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1
cilengitide 2000mgDrug
A single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1
cilengitide 1000mgDrug
A single dose of cilengitide 1000mg (125mL) will be administered as 1-hour i.v. infusion on Day 1
cilengitide > 1000mg and up to 2000mgDrug
A single dose of cilengitide > 1000mg and up to 2000mg will be administered as 1-hour i.v. infusion on Day 1 if applicable, based on Safety Monitoring Committee decision
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Healthy volunteers: matched subjects with normal renal function Receives: Drug: cilengitide 2000mg |
| Group 2 | Experimental | Mild renal impaired subjects Receives: Drug: cilengitide 2000mg |
| Group 3 | Experimental | Moderate renal impaired subjects Receives: Drug: cilengitide 2000mg |
| Group 4a | Experimental | First group of Severe renal impaired subjects Receives: Drug: cilengitide 1000mg |
| Group 4b | Experimental | Second group of severe renal impaired subjects Receives: Drug: cilengitide > 1000mg and up to 2000mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Plasma Concentration (Cmax) of cilengitide in plasma
Cmax of cilengitide in plasma after single dose in groups of subjects with different grades of renal function compared to subjects with normal renal function.
Measured: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Area under the plasma concentration versus time curve (AUC) of cilengitide in plasma
AUC of cilengitide in plasma after single dose in groups of subjects with different grades of renal function compared to subjects with normal renal function.
Measured: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Secondary outcomes (6)
Terminal half life t1/2 of cilengitide
Measured: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Plasma clearance of cilengitide (CL)
Measured: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Cilengitide volume of distribution (Vz) in plasma
Measured: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Absolute and relative amount of cilengitide excreted into urine (Ae0-∞)
Measured: 24 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Renal clearance of cilengitide (CLR)
Measured: 24 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Plasma-protein-binding: Fraction unbound of cilengitide
Measured: 2 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2012 (estimated)
- Study startJan 2012
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal ImpairmentStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andreas Becker, MD MSc, Study director, Merck Serono S.A., Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01504165
- Sponsor's protocol ID
- EMR062041_016
- Other IDs
- 2011-002389-19
- Status last verified
- Feb 2014
- First submitted
- 3 Jan 2012
- Last updated
- 4 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Parallel-group, Mono-center Trial to Investigate the Pharmacokinetics of a Single Intravenous Dose of Cilengitide in Subjects With Mild, Moderate or Severe Renal Impairment Compared to Subjects With Normal Renal Function
- ClinicalTrials.gov ID
- NCT01504165
- Acronym / sponsor ID
- EMR062041_016
- Conditions
- Renal Impairment
- Keywords
- Renal impairment, Pharmacokinetic, cilengitide, subjects with mild, moderate or severe renal impairment compared to subjects with normal renal function
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 5 Jan 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.
This is an open-label, non-randomized, parallel-group, mono-center, single intravenous dose, Phase I trial to investigate the Pharmacokinetic (PK) and safety of cilengitide in subjects with different grades of renal impairment as compared to subjects with normal renal function.
Detailed description
Subjects with impaired renal function will be screened and will be stratified by their estimated glomerular filtration rate (GFR) according to the Modification of Diet in Renal Disease (MDRD) equation and assigned to one of the stratification groups defined below:
Group Number/Renal function/Creatinine Clearance (GFR according to MDRD)
- Normal renal function (≥ 90 mL/min)
- Mild renal impairment (60 - 89 mL/min)
- Moderate renal impairment (30 - 59 mL/ min) 4a: Severe renal impairment (< 30 mL/min) - no dialysis required 4b: (if applicable) Severe renal impairment (< 30 mL/min) - no dialysis required
Subjects in Groups 2 and 3 will receive a single dose of 2000mg of cilengitide as 1-hour i.v. infusion. Subjects from group 4a will receive a single dose of 1000mg of cilengitide as 1-hour i.v. infusion . PK samples will be collected and basic PK parameters will be calculated. The safety, tolerability, and PK will be evaluated by the Safety Monitoring Committee (SMC). If the SMC has no concerns, Group 4b will be treated with a higher dose (up to 2000mg) of cilengitide. Then, Group 1 (healthy subjects) will be started after the last subject with renal impairment (in either Group 2, 3, or 4a; or in Group 4b, if applicable) has completed all activities on Day 3. They will also receive a single dose of 2000mg of cilengitide as 1-hour i.v. infusion.
The duration of the trial from the first subject enrolled to the last subject last visit will be approximately 6 months (approximately 8 months, in case Group 4b is included). Each subject will participate in the trial for up to 35 days, including screening and the end of trial examination.
Study design
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: cilengitide 2000mgHealthy volunteers: matched subjects with normal renal function |
| Group 2 | Experimental | Drug: cilengitide 2000mgMild renal impaired subjects |
| Group 3 | Experimental | Drug: cilengitide 2000mgModerate renal impaired subjects |
| Group 4a | Experimental | Drug: cilengitide 1000mgFirst group of Severe renal impaired subjects |
| Group 4b | Experimental | Drug: cilengitide > 1000mg and up to 2000mgSecond group of severe renal impaired subjects |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Body mass index (BMI): ≥ 18 kg/m² and ≤ 35 kg/m²
- Vital signs (pulse rate and blood pressure) within the normal range or showing no clinically relevant deviation
- Estimated creatinine clearance according to the MDRD equation of ≥ 90 mL/min at Screening
- Laboratory parameters should be within acceptable range for subjects with renal impairment,
- Vital signs: Pulse rate within the normal range of 45-100 beats/minute in supine position after 5 minutes of rest. Blood pressure diastolic below 100 mmHg, and systolic below 160 mmHg for Groups 1-3 and below 180 mmHg for Group 4a and 4b, in supine position after 5 minutes of rest
Key exclusion criteria (10 listed)
- History of malignant disease within the last 5 years or acute malignant disease
- Medical history of wound healing problems and/or any current open wounds
- Current or history of bleeding disorders and/or history of thromboembolic events (considering family history as well); thrombolytics or oral or parenteral anticoagulants within 30 days prior to Day 1
- Electrocardiogram recording (12-lead ECG) with signs of clinically relevant pathology as judged by the Investigator
- Chronic heart failure non stabilized (New York Heart Association [NYHA] class III and IV)
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 |
|---|---|---|
| cilengitide 2000mgA single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1 | Drug | Group 1 |
| cilengitide 2000mgA single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1 | Drug | Group 2 |
| cilengitide 2000mgA single dose of cilengitide 2000mg (250mL) will be administered as 1-hour i.v. infusion on Day 1 | Drug | Group 3 |
| cilengitide 1000mgA single dose of cilengitide 1000mg (125mL) will be administered as 1-hour i.v. infusion on Day 1 | Drug | Group 4a |
| cilengitide > 1000mg and up to 2000mgA single dose of cilengitide > 1000mg and up to 2000mg will be administered as 1-hour i.v. infusion on Day 1 if applicable, based on Safety Monitoring Committee decision | Drug | Group 4b |
Primary outcome
Peak Plasma Concentration (Cmax) of cilengitide in plasma
Time frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Cmax of cilengitide in plasma after single dose in groups of subjects with different grades of renal function compared to subjects with normal renal function.
Area under the plasma concentration versus time curve (AUC) of cilengitide in plasma
Time frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
AUC of cilengitide in plasma after single dose in groups of subjects with different grades of renal function compared to subjects with normal renal function.
6 secondary outcomes
Terminal half life t1/2 of cilengitide
Time frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Plasma clearance of cilengitide (CL)
Time frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Cilengitide volume of distribution (Vz) in plasma
Time frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Absolute and relative amount of cilengitide excreted into urine (Ae0-∞)
Time frame: 24 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Renal clearance of cilengitide (CLR)
Time frame: 24 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
Plasma-protein-binding: Fraction unbound of cilengitide
Time frame: 2 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion
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 4 Feb 2014.
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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.
Andreas Becker, MD MSc study director
Merck Serono S.A., Geneva
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cilengitide 2000mg, cilengitide 1000mg and cilengitide > 1000mg and up to 2000mg in people with Renal Impairment, run by Merck KGaA, Darmstadt, Germany at 2 sites in Germany.
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 10 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 4 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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?
Peak Plasma Concentration (Cmax) of cilengitide in plasma (time frame: 48 hours after start of infusion of 1 single dose of cilengitide administered as 1-hour intravenous infusion). 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?
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 4 Feb 2014.