<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03785613</url>
  </required_header>
  <id_info>
    <org_study_id>HP5303/05</org_study_id>
    <nct_id>NCT03785613</nct_id>
  </id_info>
  <brief_title>Clinical Pilot Study in Healthy Men to Characterize the Uptake of Buprenorphine Into and Its Elimination From the Body After Topical Application of Two New Forms of a Skin Patch in Comparison to a Reference Patch</brief_title>
  <official_title>Pilot Study to Investigate the Pharmacokinetic Characteristics of Two Buprenorphine Transdermal Patch Formulations as Compared to a Reference Patch</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grünenthal GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Grünenthal GmbH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is intended to produce information on the pharmacokinetic characteristics (uptake&#xD;
      into and elimination from the body) of two new patch formulations of the analgesic&#xD;
      buprenorphine as compared to the reference patch Transtec (Registered Trademark) 35&#xD;
      micrograms per hour (μg/h) in order to assess the suitability of the test formulations for a&#xD;
      later confirmatory bioequivalence study.&#xD;
&#xD;
      In addition to a reduced buprenorphine load, the new patch formulations may potentially&#xD;
      provide improved wearing properties. A placebo patch formulation of the respective test or&#xD;
      reference patch will be applied simultaneously to explore the skin tolerability and skin&#xD;
      adhesiveness of the patch formulations. Furthermore, the safety and tolerability of the&#xD;
      treatments will be assessed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 7, 2005</start_date>
  <completion_date type="Actual">March 14, 2006</completion_date>
  <primary_completion_date type="Actual">March 14, 2006</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>3-way cross-over (three periods, three treatments and six sequence groups) with single application each. There will be a wash-out period between administrations, i.e., between removal of previous patch and application of new patch of at least 10 days.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the concentration-time extrapolated to infinity (AUC)</measure>
    <time_frame>pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose</time_frame>
    <description>For the analysis of buprenorphine in human plasma a liquid chromatography-double quadrupole mass spectrometry (LC-MS/MS)-validated method will be used. AUC is calculated by summation of the partial areas AUC(0-t) and the residual area AUC(t-∞) represents the recalculated plasma concentration at the last sampling time point with a quantifiable concentration. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve up the last quantifiable plasma concentration (AUC0-t)</measure>
    <time_frame>pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose</time_frame>
    <description>Area under data from administration until the last sampling point (tz) with a quantifiable concentration, calculated by the linear/log trapezoidal method, i.e., the linear trapezoidal rule is applied up to Cmax and then the log trapezoidal rule is applied for the remainder of the curve. If multiple maxima are observed in the concentration-time curve, Cmax is assigned to the first maximum. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma concentration (Cmax) of buprenorphine</measure>
    <time_frame>pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose</time_frame>
    <description>Maximum plasma concentration, highest observed plasma concentration of the measured concentration-time profile. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to attain maximum plasma concentration (tmax)</measure>
    <time_frame>pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose</time_frame>
    <description>Time of maximum concentration, time after administration at which Cmax occurs. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lag-time observed from dosing to the time-point prior to the first quantifiable plasma concentration (tlag)</measure>
    <time_frame>pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose</time_frame>
    <description>Lag-time observed from dosing to the time-point prior to the first quantifiable plasma concentration. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t1/2,z)</measure>
    <time_frame>pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose</time_frame>
    <description>Apparent terminal elimination half-life. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of skin adhesiveness</measure>
    <time_frame>Day 1 to Day 5</time_frame>
    <description>Reading of skin adhesiveness of the patch will be performed for test/reference and placebo administration sites each on Days 1-5 (every 12 hours following patch application and at 96 hours following patch application immediately before patch removal).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of skin irritation</measure>
    <time_frame>At baseline, on Days 1-5 (immediately and 20 min following patch removal), on Days 8-10 (120 hours following patch application)</time_frame>
    <description>Assessment of skin irritation will be performed (for test/reference and placebo patch each) at baseline, on Days 1-5 (immediately and 20 min following patch removal), and on Days 8-10 (120 hours following patch application).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment emergent adverse events</measure>
    <time_frame>From Day 1 (patch application) until Day 12 (Final examination)</time_frame>
    <description>Number of adverse events and participants with adverse events.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Test Product T1: Buprenorphine patch (9 mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Buprenorphine transdermal patch formulation, containing 9 milligrams buprenorphine in an active surface area of 25 square centimeters. Single application of transdermal patch during 96 hours, on skin in the midclavicular line directly under the clavicle.&#xD;
Matching placebo patch to T1: simultaneous application for 96 hours on the upper back.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Test Product T2: Buprenorphine patch (3.8 mg)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Buprenorphine transdermal patch formulation, containing 3.8 milligrams buprenorphine in an active surface area of 10 square centimeters. Single application of patch during 96 hours, on skin in the midclavicular line directly under the clavicle.&#xD;
Matching placebo patch to T2: simultaneous application for 96 hours on the upper back.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reference Product R: Transtec patch (20 mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Transtec (Registered Trademark) transdermal patch containing 20 milligrams buprenorphine in an active surface area of 25 square centimeters. Single application of transdermal patch during 96 hours, on skin in the midclavicular line directly under the clavicle.&#xD;
Matching placebo patch to R: simultaneous application for 96 hours on the upper back.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Test Product T1: Buprenorphine patch (9 mg)</intervention_name>
    <description>Buprenorphine transdermal patch formulation, containing 9 milligrams buprenorphine in an active surface area of 25 square centimeters.</description>
    <arm_group_label>Test Product T1: Buprenorphine patch (9 mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Test Product T2: Buprenorphine patch (3.8 mg)</intervention_name>
    <description>Buprenorphine transdermal patch formulation, containing 3.8 milligrams buprenorphine in an active surface area of 10 square centimeters.</description>
    <arm_group_label>Test Product T2: Buprenorphine patch (3.8 mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Reference Product R: Transtec patch (20 mg)</intervention_name>
    <description>Transtec (Registered Trademark) transdermal patch containing 20 milligrams buprenorphine in an active surface area of 25 square centimeters, release rate 35 micrograms per hour.</description>
    <arm_group_label>Reference Product R: Transtec patch (20 mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Matching placebo patch to T1</intervention_name>
    <description>Placebo patch to T1.</description>
    <arm_group_label>Test Product T1: Buprenorphine patch (9 mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Matching placebo patch to T2</intervention_name>
    <description>Placebo patch to T2.</description>
    <arm_group_label>Test Product T2: Buprenorphine patch (3.8 mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Matching placebo patch to R</intervention_name>
    <description>Placebo patch to R.</description>
    <arm_group_label>Reference Product R: Transtec patch (20 mg)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male Caucasian participants aged 18-55 years.&#xD;
&#xD;
          -  Body mass index (BMI) between 18 and 30 kilograms per square meter inclusive.&#xD;
&#xD;
          -  Participants must be in good health as determined by medical history, physical&#xD;
             examination, 12-lead electrocardiogram, vital signs, and clinical laboratory&#xD;
             parameters.&#xD;
&#xD;
          -  Participants giving written informed consent to participate within this trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Resting pulse rate less than or equal to 45 or greater than or equal to 95 beats per&#xD;
             minute (participant has rested in the sitting position for at least 3 minutes).&#xD;
&#xD;
          -  Resting blood pressure (participant has rested in the sitting position for at least 3&#xD;
             minutes) systolic blood pressure less than or equal to 100 and greater than or equal&#xD;
             to 140 millimeters mercury (mmHg), diastolic blood pressure less than or equal to 50&#xD;
             and greater than or equal to 95 mmHg.&#xD;
&#xD;
          -  Positive human immunodeficiency virus (HIV) type 1/2 antibodies, hepatitis B surface&#xD;
             (HBs) antigen, hepatitis B core (HBc) antibodies, hepatitis C virus (HCV) antibodies.&#xD;
&#xD;
          -  History or presence of orthostatic hypotension.&#xD;
&#xD;
          -  Participation in another clinical study in the last three months before starting this&#xD;
             study (exception: characterization of metabolizer status).&#xD;
&#xD;
          -  Positive drug of abuse screening (amphetamines, tetrahydrocannabinol [THC], cocaine,&#xD;
             morphines, or positive breath alcohol) at screening or baseline.&#xD;
&#xD;
          -  Diseases or condition known to interfere with the absorption, distribution, metabolism&#xD;
             or excretion of drugs.&#xD;
&#xD;
          -  Marked repolarization abnormality (e.g., suspicious or definite congenital long QT&#xD;
             syndrome) or co-medication that is known to influence cardiac repolarization&#xD;
             substantially.&#xD;
&#xD;
          -  Bronchial asthma.&#xD;
&#xD;
          -  Definite or suspected history of drug allergy or hypersensitivity, especially known&#xD;
             sensitivity to buprenorphine, naltrexone or naloxone.&#xD;
&#xD;
          -  Patch allergy.&#xD;
&#xD;
          -  Participants who have received any prescribed and non-prescribed systemic or topical&#xD;
             medication two weeks before and during the study with the exception of short term&#xD;
             medication, e.g. paracetamol for the treatment of headache.&#xD;
&#xD;
          -  History or suspicion of alcohol or drug abuse, e.g., use of barbiturates,&#xD;
             amphetamines, ecstasy, meta-chlorophenylpiperazine (mCPP), cannabis, or narcotics.&#xD;
&#xD;
          -  Not able to abstain from drinking of caffeine containing beverages (tea, coffee,&#xD;
             chocolate, or cola).&#xD;
&#xD;
          -  Consumption of any quinine containing beverages (bitter lemon, tonic water) or food&#xD;
             within two weeks before and during the study.&#xD;
&#xD;
          -  Drinking of alcohol containing beverages within 48 hours before administration of&#xD;
             investigational product(s).&#xD;
&#xD;
          -  Blood donation or comparable blood loss (more than 100 milliliters) during the last 3&#xD;
             months.&#xD;
&#xD;
          -  History of seizures or at risk (i.e., head trauma, epilepsy in family anamnesis,&#xD;
             unclear loss of consciousness).&#xD;
&#xD;
          -  Known or suspected of not being able to comply with the study protocol.&#xD;
&#xD;
          -  Not able to communicate meaningfully with the investigator and staff.&#xD;
&#xD;
          -  Smoking of more than 20 cigarettes per day or equivalent.&#xD;
&#xD;
          -  History of any disorder of the respiratory center.&#xD;
&#xD;
          -  Unhealthy skin according to examination by the study physician, not allowing proper&#xD;
             patch administration.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Grünenthal Study Director</last_name>
    <role>Study Director</role>
    <affiliation>Grünenthal GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Swiss Pharma Contract</name>
      <address>
        <city>Allschwil</city>
        <zip>4123</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>December 20, 2018</last_update_submitted>
  <last_update_submitted_qc>December 20, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Buprenorphine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03785613
org study id: HP5303/05
nct id: NCT03785613
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is intended to produce information on the pharmacokinetic characteristics (uptake
      into and elimination from the body) of two new patch formulations of the analgesic
      buprenorphine as compared to the reference patch Transtec (Registered Trademark) 35
      micrograms per hour (μg/h) in order to assess the suitability of the test formulations for a
      later confirmatory bioequivalence study.

      In addition to a reduced buprenorphine load, the new patch formulations may potentially
      provide improved wearing properties. A placebo patch formulation of the respective test or
      reference patch will be applied simultaneously to explore the skin tolerability and skin
      adhesiveness of the patch formulations. Furthermore, the safety and tolerability of the
      treatments will be assessed.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: 3-way cross-over (three periods, three treatments and six sequence groups) with single application each. There will be a wash-out period between administrations, i.e., between removal of previous patch and application of new patch of at least 10 days.
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the concentration-time extrapolated to infinity (AUC)
time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
description: For the analysis of buprenorphine in human plasma a liquid chromatography-double quadrupole mass spectrometry (LC-MS/MS)-validated method will be used. AUC is calculated by summation of the partial areas AUC(0-t) and the residual area AUC(t-∞) represents the recalculated plasma concentration at the last sampling time point with a quantifiable concentration. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
measure: Area under the concentration-time curve up the last quantifiable plasma concentration (AUC0-t)
time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
description: Area under data from administration until the last sampling point (tz) with a quantifiable concentration, calculated by the linear/log trapezoidal method, i.e., the linear trapezoidal rule is applied up to Cmax and then the log trapezoidal rule is applied for the remainder of the curve. If multiple maxima are observed in the concentration-time curve, Cmax is assigned to the first maximum. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
measure: Maximum plasma concentration (Cmax) of buprenorphine
time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
description: Maximum plasma concentration, highest observed plasma concentration of the measured concentration-time profile. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
measure: Time to attain maximum plasma concentration (tmax)
time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
description: Time of maximum concentration, time after administration at which Cmax occurs. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
measure: Lag-time observed from dosing to the time-point prior to the first quantifiable plasma concentration (tlag)
time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
description: Lag-time observed from dosing to the time-point prior to the first quantifiable plasma concentration. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
measure: Terminal half-life (t1/2,z)
time frame: pre-dose, and after 4, 8, 12, 16, 24, 36, 48, 60, 72, 80, 88, 96, 104, 112, 120, 132, 144, 156, and 168 hours post-dose
description: Apparent terminal elimination half-life. Blood sampling for the determination of the plasma concentrations will be performed at the following time points:
measure: Assessment of skin adhesiveness
time frame: Day 1 to Day 5
description: Reading of skin adhesiveness of the patch will be performed for test/reference and placebo administration sites each on Days 1-5 (every 12 hours following patch application and at 96 hours following patch application immediately before patch removal).
measure: Assessment of skin irritation
time frame: At baseline, on Days 1-5 (immediately and 20 min following patch removal), on Days 8-10 (120 hours following patch application)
description: Assessment of skin irritation will be performed (for test/reference and placebo patch each) at baseline, on Days 1-5 (immediately and 20 min following patch removal), and on Days 8-10 (120 hours following patch application).
measure: Incidence of treatment emergent adverse events
time frame: From Day 1 (patch application) until Day 12 (Final examination)
description: Number of adverse events and participants with adverse events.
arm group label: Test Product T1: Buprenorphine patch (9 mg)
arm group type: Experimental
description: Buprenorphine transdermal patch formulation, containing 9 milligrams buprenorphine in an active surface area of 25 square centimeters. Single application of transdermal patch during 96 hours, on skin in the midclavicular line directly under the clavicle.
Matching placebo patch to T1: simultaneous application for 96 hours on the upper back.
arm group label: Test Product T2: Buprenorphine patch (3.8 mg)
arm group type: Experimental
description: Buprenorphine transdermal patch formulation, containing 3.8 milligrams buprenorphine in an active surface area of 10 square centimeters. Single application of patch during 96 hours, on skin in the midclavicular line directly under the clavicle.
Matching placebo patch to T2: simultaneous application for 96 hours on the upper back.
arm group label: Reference Product R: Transtec patch (20 mg)
arm group type: Active Comparator
description: Transtec (Registered Trademark) transdermal patch containing 20 milligrams buprenorphine in an active surface area of 25 square centimeters. Single application of transdermal patch during 96 hours, on skin in the midclavicular line directly under the clavicle.
Matching placebo patch to R: simultaneous application for 96 hours on the upper back.
intervention type: Drug
intervention name: Test Product T1: Buprenorphine patch (9 mg)
description: Buprenorphine transdermal patch formulation, containing 9 milligrams buprenorphine in an active surface area of 25 square centimeters.
arm group label: Test Product T1: Buprenorphine patch (9 mg)
intervention type: Drug
intervention name: Test Product T2: Buprenorphine patch (3.8 mg)
description: Buprenorphine transdermal patch formulation, containing 3.8 milligrams buprenorphine in an active surface area of 10 square centimeters.
arm group label: Test Product T2: Buprenorphine patch (3.8 mg)
intervention type: Drug
intervention name: Reference Product R: Transtec patch (20 mg)
description: Transtec (Registered Trademark) transdermal patch containing 20 milligrams buprenorphine in an active surface area of 25 square centimeters, release rate 35 micrograms per hour.
arm group label: Reference Product R: Transtec patch (20 mg)
intervention type: Drug
intervention name: Matching placebo patch to T1
description: Placebo patch to T1.
arm group label: Test Product T1: Buprenorphine patch (9 mg)
intervention type: Drug
intervention name: Matching placebo patch to T2
description: Placebo patch to T2.
arm group label: Test Product T2: Buprenorphine patch (3.8 mg)
intervention type: Drug
intervention name: Matching placebo patch to R
description: Placebo patch to R.
arm group label: Reference Product R: Transtec patch (20 mg)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Grünenthal Study Director
role: Study Director
affiliation: Grünenthal GmbH
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Buprenorphine
sharing ipd: No