Phase 1: Pain Management, Phase 2: Pain Management
Conditions
Brief summary
Two-part study of intrathecal paracetamol administered immediately before spinal anaesthesia in patients scheduled for hip replacement surgery
Detailed description
This is a prospective, single centre, two-part, three doses study. Part 1 is a Phase I, three cohorts, dose-ascending, open-label, safety study. Part 2 is a Phase II, randomised, parallel-group, double-blind, placebo-controlled, exploratory efficacy and safety study The objective of the study is to investigate the efficacy and safety of a single intrathecal injection of paracetamol, administered at 3 doses to 3 active treatment groups, as compared to placebo solution, for post-operative analgesia of hip replacement surgery performed under spinal anaesthesia. Patients scheduled for hip replacement surgery will be randomised into 4 treatment groups (15 patients per group) to receive either one of the 3 single doses of paracetamol 3% (D1: 60 mg, D2: 90 mg, D3: 120 mg) or placebo solution (P: saline solution) by intrathecal (IT) injection. Immediately after paracetamol or placebo IT administration, all patients will receive a single IT dose of Hyperbaric Bupivacaine HCl 0.5% (12.5 mg for ≤ 160 cm-tall patients and 15 mg for \> 160 cm-tall patients). The time interval between paracetamol IT and bupivacaine IT administrations should not exceed 2 min. The study will include a screening phase (Visit 1, Days -21/1), a treatment phase (paracetamol IT administration, anaesthesia and surgical procedure: Visit 2, Day 1) and a follow-up phase including an observation period (Visit 3, from Day 1 after surgery until discharge, a final visit (at discharge) and a follow-up (day 6±1). Pain at rest will be assessed at screening and on visit 2 at baseline (0 h), 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45 and 48 h after anaesthetic IT injection and at discharge, using a 0-100 mm VAS.
Interventions
DRUGParacetamol 3%
Investigate the efficacy and safety of a single intrathecal injection of paracetamol,for post-operative analgesia of hip replacement surgery
DRUGPlacebo injection containing Saline solution 0.9%
Injection containing sterile solution of Saline Solution 0.9 %. Study part 2 will be placebo-controlled. Each patient will be allocated to a treatment arm (one of the three paracetamol doses or placebo) according to a computer-generated randomisation list.
DRUGHyperbaric Bupivacaine HCl 0.5%
NIMP, spinal anaesthetic before the surgical procedure
Sponsors
Cross S.A.
Sintetica SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Masking description
Phase II only
Intervention model description
4 arms for Phase II only
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Phase 1 and Phase 2: * Informed consent: signed written informed consent before inclusion in the study * Sex, age and surgery: male/female 18-80 years (inclusive) old patients, scheduled for hip replacement surgery, with anticipated need for post-operative narcotic analgesia, adequate i.v. access and anticipated hospital stay \> 48 hours. * Body Mass Index (BMI): 18 - 34 kg/m2 inclusive * ASA physical status: I-III * Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study * Inclusion criteria - Phase 1 only : Age: 18-70 (inclusive) old patients * Inclusion criteria - Phase 2 only : Age: 18-80 (inclusive) old patients Hospital stay: Patients with anticipated hospital stay \> 48 hours
Exclusion criteria
Phase 1 and Phase 2: * Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study. Contraindications to spinal anaesthesia. History of neuromuscular diseases to the lower extremities * ASA physical status: IV-V * Further anaesthesia: patients expected to require further anaesthesia * Pain assessment: anticipated to be unable to make a reliable self-report of pain intensity * Allergy: ascertained or presumptive hypersensitivity to the active principles (paracetamol and/or amide type anaesthetics) and/or formulations' ingredients or related drugs, opioids, non-steroidal anti-inflammatory drugs; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers could affect the outcome of the study * Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that may interfere with the aim of the study; ascertained psychiatric and neurological diseases, sepsis, blood coagulation disorders, severe cardiopulmonary disease, thyroid disease, diabetes, other neuropathies, history or evidence of asthma or heart failure. History of severe head trauma that required hospitalisation, intracranial surgery or stroke within the previous 30 days, or any history of intracerebral arteriovenous malformation, cerebral aneurism or CNS mass lesion. * Liver function: Impaired liver function (transaminases \> twice upper limit) * Renal function: Renal dysfunction (creatinine \> 2.0 mg/dL) * Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study, calculated from the first day of the month following the last visit of the previous study * Drug, alcohol: history of drug or alcohol abuse. Pre-existing dependence on narcotics or known tolerance to opioids * Pregnancy and lactation: positive pregnancy test at screening (if applicable), pregnant or lactating women \[The pregnancy test will be performed to all fertile women and to all women up to 55 years old, if not in proven menopause (available laboratory test confirming menopause or surgically sterilised)\] * Chronic pain syndromes: patients with chronic pain syndromes (taking opioids, anticonvulsant agents or chronic analgesic therapy). * Medications: medication known to interfere with the extent of spinal blocks for 2 weeks before the start of the study. Paracetamol formulations, other than the investigational product, for 1 week before the start of the study and during the study. Hormonal contraceptives for females are allowed. * Phase 2 only -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | In the first 24 hours, in the first 48 hours and at day 7±1 | Phase 1: Number of participants with treatment evaluation and confirmation of the safety of the three doses of paracetamol 3% solution administered in the total number of patients enrolled |
| Phase 2: Pain Intensity | baseline (0 h), 1, 6, 9, 12, 15, 24, and 48 h after anaesthetic IT injection and at discharge | Phase 2: Pain intensity at rest evaluated as VAS scores ( 0-100 mm visual analogue scale : 0 is the absence pain and 100 is the maximum pain sensation) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Number of Participants With Need for Supplemental Analgesia | Postoperative, up to 48 hours after end of surgery | Phase 2: Need for supplementary analgesia, other than the planned morphine PCA |
| Phase 2: Morphine-related Adverse Events | up to 24 hours after surgery, up to 48 hours | Percentage of subjects experiencing during the study the morphine-related adverse events pre-specified in the protocol |
| Phase 2: Time to Readiness for Surgery | Intraoperative | Time period from completion of spinal injection (time 0 h) to achievement of sensory and motor block adequate for surgery. |
| Phase 2:Maximum Level of Sensory Block | Intraoperative | Sensorial block will be verified by bilateral Pinprick test using a 20-G hypodermic needle and will be recorded. Pinprick sensation will be scored as being present (score 1) or absent (score 0). Onset of sensory block is defined as an absent touch sensation (score 0) |
| Phase 2: Time to Sensory Block | Intraoperative | Time to maximum level of sensory block |
| Phase 2: Morphine | At 24 and 48 h after anaesthetic IT injection and entire study period, up to 7 days | Phase 2: Total morphine use |
| Phase 2: Vital Signs | at screening, at baseline (before the spinal injection) and at end of the study (Day 6). | Systolic and Diastolic Blood Pressure (mmHg) |
| Phase2: Concomitant Medications | at screening, at baseline until the end of the study (Day 6) | record the concomitant medications intaked during the study |
| Phase 2: SpO2 | at screening, at baseline (before the spinal injection) and at the end of the study (day 6) | Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the blood. |
| Phase 2: ECG | screening, baseline and end of study (Day 6±1) | Electrocardiography is the process of producing an electrocardiogram (ECG), it is a graph of voltage versus time of the electrical activity of the heart using electrodes placed on the skin. |
| Phase 2: Time to Regression of Spinal Block | from readiness for surgery,then every 10 min until the maximum level is reached (two consecutive observations with the same level of sensory block) and then every 30 min until regression of spinal block | Time period from spinal injection (time 0 h) to the time when the Bromage score returns to 0 and sensitive perception returns to S1. Bromage scale: I - Free movement of legs and feet II - Just able to flex knees with free movement of feet III - Unable to flex knees, but with free movement of feet IV - Unable to move legs or feet |
| Phase 2: Time to First Morphine Use | Postoperative, up to 48 hours after end of surgery | Phase 2: Time to first morphine use (minutes) |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 60 mg Paracetamol 3% (2 mL) 60 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.
Paracetamol 3%: Investigate the efficacy and safety of a single intrathecal injection of paracetamol,for post-operative analgesia of hip replacement surgery
Hyperbaric Bupivacaine HCl 0.5%: NIMP, spinal anaesthetic before the surgical procedure | 18 |
| 90 mg Paracetamol 3% (3 mL) 90 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.
Paracetamol 3%: Investigate the efficacy and safety of a single intrathecal injection of paracetamol,for post-operative analgesia of hip replacement surgery
Hyperbaric Bupivacaine HCl 0.5%: NIMP, spinal anaesthetic before the surgical procedure | 18 |
| 120 mg Paracetamol 3% (4mL) 120 mg Paracetamol 3%. Solution for injection, single administration by Intrathecal route.
Paracetamol 3%: Investigate the efficacy and safety of a single intrathecal injection of paracetamol,for post-operative analgesia of hip replacement surgery
Hyperbaric Bupivacaine HCl 0.5%: NIMP, spinal anaesthetic before the surgical procedure | 18 |
| Phase II Only: Saline Solution 0.9% Placebo, 0.9%. Solution for injection , single administration by route Intrathecal (2 mL, 3 mL and 4 mL) Study part 2 will be placebo-controlled. Each patient will be allocated to a treatment arm (one of the three paracetamol doses or placebo) according to a computer-generated randomisation list.
Placebo injection containing Saline solution 0.9%: Injection containing sterile solution of Saline Solution 0.9 %.
Study part 2 will be placebo-controlled. Each patient will be allocated to a treatment arm (one of the three paracetamol doses or placebo) according to a computer-generated randomisation list.
Hyperbaric Bupivacaine HCl 0.5%: NIMP, spinal anaesthetic before the surgical procedure | 15 |
| Total | 69 |
Baseline characteristics
| Characteristic | 60 mg Paracetamol 3% (2 mL) | Total | Phase II Only: Saline Solution 0.9% | 120 mg Paracetamol 3% (4mL) | 90 mg Paracetamol 3% (3 mL) |
|---|---|---|---|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 6.7 | 64.8 years STANDARD_DEVIATION 7.9 | 65.1 years STANDARD_DEVIATION 7.7 | 62.3 years STANDARD_DEVIATION 9.3 | 65.1 years STANDARD_DEVIATION 7.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 69 Participants | 15 Participants | 18 Participants | 18 Participants |
| Sex: Female, Male Female | 8 Participants | 31 Participants | 6 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 10 Participants | 38 Participants | 9 Participants | 14 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 15 |
| other Total, other adverse events | 8 / 18 | 10 / 18 | 13 / 18 | 11 / 15 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 | 0 / 15 |
Outcome results
Primary
Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol
Phase 1: Number of participants with treatment evaluation and confirmation of the safety of the three doses of paracetamol 3% solution administered in the total number of patients enrolled
Time frame: In the first 24 hours, in the first 48 hours and at day 7±1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | Adverse event not related | 1 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | Adverse event related | 0 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | Serious adverse event | 0 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | Adverse event not related | 1 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | Adverse event related | 0 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | Serious adverse event | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | Adverse event related | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | Serious adverse event | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 1: Number of Participants With Adverse Events Related, Not Related and Serious Events Related to Paracetamol | Adverse event not related | 6 participants |
Primary
Phase 2: Pain Intensity
Phase 2: Pain intensity at rest evaluated as VAS scores ( 0-100 mm visual analogue scale : 0 is the absence pain and 100 is the maximum pain sensation)
Time frame: baseline (0 h), 1, 6, 9, 12, 15, 24, and 48 h after anaesthetic IT injection and at discharge
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Pain Intensity | 12 hours after anaesthetic | 13.1 units on a scale | Standard Deviation 16.5 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Pain Intensity | 15 hours after anaesthetic | 15.4 units on a scale | Standard Deviation 16.7 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Pain Intensity | 1 hour after anaesthetic | 0 units on a scale | Standard Deviation 0 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Pain Intensity | 24 hours after anaesthetic | 11.4 units on a scale | Standard Deviation 10.7 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Pain Intensity | Discharge | 2.5 units on a scale | Standard Deviation 3.7 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Pain Intensity | 6 hours after anaesthetic | 21.5 units on a scale | Standard Deviation 22.2 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Pain Intensity | baseline | 11.9 units on a scale | Standard Deviation 15.5 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Pain Intensity | 9 hours after anaesthetic | 21.6 units on a scale | Standard Deviation 18 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Pain Intensity | 48 hours after anaesthetic | 6.1 units on a scale | Standard Deviation 8.6 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Pain Intensity | 9 hours after anaesthetic | 13.6 units on a scale | Standard Deviation 11.6 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Pain Intensity | 24 hours after anaesthetic | 9.5 units on a scale | Standard Deviation 8.9 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Pain Intensity | 6 hours after anaesthetic | 32.2 units on a scale | Standard Deviation 25 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Pain Intensity | 15 hours after anaesthetic | 10.2 units on a scale | Standard Deviation 10.2 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Pain Intensity | Discharge | 4.1 units on a scale | Standard Deviation 4.8 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Pain Intensity | 48 hours after anaesthetic | 3.2 units on a scale | Standard Deviation 6.6 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Pain Intensity | 1 hour after anaesthetic | 0 units on a scale | Standard Deviation 0 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Pain Intensity | baseline | 17.3 units on a scale | Standard Deviation 15.6 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Pain Intensity | 12 hours after anaesthetic | 10.1 units on a scale | Standard Deviation 8.6 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Pain Intensity | 12 hours after anaesthetic | 11.2 units on a scale | Standard Deviation 17.5 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Pain Intensity | baseline | 24.5 units on a scale | Standard Deviation 19.5 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Pain Intensity | 1 hour after anaesthetic | 0 units on a scale | Standard Deviation 0 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Pain Intensity | 6 hours after anaesthetic | 20.3 units on a scale | Standard Deviation 25.3 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Pain Intensity | 9 hours after anaesthetic | 17.3 units on a scale | Standard Deviation 24 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Pain Intensity | 15 hours after anaesthetic | 10.6 units on a scale | Standard Deviation 13.8 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Pain Intensity | 24 hours after anaesthetic | 13.6 units on a scale | Standard Deviation 14.9 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Pain Intensity | 48 hours after anaesthetic | 7.7 units on a scale | Standard Deviation 12.9 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Pain Intensity | Discharge | 4.8 units on a scale | Standard Deviation 6.8 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Pain Intensity | 24 hours after anaesthetic | 16 units on a scale | Standard Deviation 18.3 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Pain Intensity | 9 hours after anaesthetic | 26.3 units on a scale | Standard Deviation 22.3 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Pain Intensity | 6 hours after anaesthetic | 42.3 units on a scale | Standard Deviation 31.5 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Pain Intensity | Discharge | 8.0 units on a scale | Standard Deviation 9.6 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Pain Intensity | 48 hours after anaesthetic | 8.7 units on a scale | Standard Deviation 11.6 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Pain Intensity | 1 hour after anaesthetic | 0 units on a scale | Standard Deviation 0 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Pain Intensity | 15 hours after anaesthetic | 20.5 units on a scale | Standard Deviation 21.5 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Pain Intensity | 12 hours after anaesthetic | 17.9 units on a scale | Standard Deviation 16.7 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Pain Intensity | baseline | 10.7 units on a scale | Standard Deviation 13.4 |
Secondary
Phase2: Concomitant Medications
record the concomitant medications intaked during the study
Time frame: at screening, at baseline until the end of the study (Day 6)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Acetic acid derivatives and related substances | 6 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Natural opium alkaloids | 0 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Osmotically acting laxatives | 1 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Solutions affecting the electrolyte balance | 15 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Benzodiazepine derivatives | 2 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Proton pump inhibitors | 2 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | heparin group | 15 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Serotonin (5HT3) antagonists | 1 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Direct factor Xa inhibi | 15 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Amino acids | 14 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Platelet aggregation inhibitors excl. heparin | 1 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | propofol | 11 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Second-generation cephalosporins | 15 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Adrenergic and dopaminergic agents | 10 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Other opioids | 1 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Propionic acid derivatives | 7 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Angiotensin II antagonists, | 1 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | Pyrazolones | 4 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase2: Concomitant Medications | ANTIEMETICS AND ANTINAUSEANTS | 1 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Adrenergic and dopaminergic agents | 11 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Amino acids | 13 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Benzodiazepine derivatives | 0 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Natural opium alkaloids | 0 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Osmotically acting laxatives | 3 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Second-generation cephalosporins | 15 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Acetic acid derivatives and related substances | 7 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | propofol | 13 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Proton pump inhibitors | 4 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | ANTIEMETICS AND ANTINAUSEANTS | 2 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Serotonin (5HT3) antagonists | 6 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Other opioids | 1 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Solutions affecting the electrolyte balance | 15 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | heparin group | 15 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Angiotensin II antagonists, | 1 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Propionic acid derivatives | 8 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Direct factor Xa inhibi | 15 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Pyrazolones | 7 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase2: Concomitant Medications | Platelet aggregation inhibitors excl. heparin | 1 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Proton pump inhibitors | 4 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Pyrazolones | 11 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | heparin group | 15 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Second-generation cephalosporins | 15 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Solutions affecting the electrolyte balance | 15 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Direct factor Xa inhibi | 14 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Amino acids | 12 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | propofol | 13 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Adrenergic and dopaminergic agents | 12 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Propionic acid derivatives | 10 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Acetic acid derivatives and related substances | 8 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Osmotically acting laxatives | 6 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Serotonin (5HT3) antagonists | 2 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Benzodiazepine derivatives | 4 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | ANTIEMETICS AND ANTINAUSEANTS | 1 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Other opioids | 1 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Platelet aggregation inhibitors excl. heparin | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Angiotensin II antagonists, | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase2: Concomitant Medications | Natural opium alkaloids | 1 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Pyrazolones | 9 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Propionic acid derivatives | 6 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Angiotensin II antagonists, | 0 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | ANTIEMETICS AND ANTINAUSEANTS | 3 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Adrenergic and dopaminergic agents | 12 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | propofol | 14 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Second-generation cephalosporins | 15 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Other opioids | 2 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Amino acids | 15 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Direct factor Xa inhibi | 15 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | heparin group | 15 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Platelet aggregation inhibitors excl. heparin | 1 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Proton pump inhibitors | 3 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Solutions affecting the electrolyte balance | 15 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Serotonin (5HT3) antagonists | 4 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Osmotically acting laxatives | 3 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Acetic acid derivatives and related substances | 8 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Natural opium alkaloids | 1 participants |
| Phase II Only: Saline Solution 0.9% | Phase2: Concomitant Medications | Benzodiazepine derivatives | 2 participants |
Secondary
Phase 2: ECG
Electrocardiography is the process of producing an electrocardiogram (ECG), it is a graph of voltage versus time of the electrical activity of the heart using electrodes placed on the skin.
Time frame: screening, baseline and end of study (Day 6±1)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: ECG | end of study | normal | 12 Participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: ECG | baseline | Abnormal, Clinically Significant | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: ECG | end of study | Abnormal, Clinically Significant | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: ECG | baseline | normal | 13 Participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: ECG | screening | Abnormal, Clinically Significant | 0 Participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: ECG | screening | Abnormal, Not Clinically Significant | 5 Participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: ECG | end of study | Abnormal, Not Clinically Significant | 3 Participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: ECG | baseline | Abnormal, Not Clinically Significant | 2 Participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: ECG | screening | normal | 10 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: ECG | baseline | Abnormal, Not Clinically Significant | 4 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: ECG | end of study | normal | 13 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: ECG | baseline | Abnormal, Clinically Significant | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: ECG | screening | Abnormal, Not Clinically Significant | 6 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: ECG | screening | normal | 9 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: ECG | screening | Abnormal, Clinically Significant | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: ECG | end of study | Abnormal, Clinically Significant | 0 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: ECG | end of study | Abnormal, Not Clinically Significant | 2 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: ECG | baseline | normal | 11 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: ECG | baseline | Abnormal, Not Clinically Significant | 4 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: ECG | screening | normal | 11 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: ECG | screening | Abnormal, Not Clinically Significant | 4 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: ECG | screening | Abnormal, Clinically Significant | 0 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: ECG | baseline | normal | 11 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: ECG | baseline | Abnormal, Clinically Significant | 0 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: ECG | end of study | normal | 11 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: ECG | end of study | Abnormal, Not Clinically Significant | 4 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: ECG | end of study | Abnormal, Clinically Significant | 0 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: ECG | end of study | normal | 12 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: ECG | baseline | normal | 12 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: ECG | screening | Abnormal, Clinically Significant | 0 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: ECG | end of study | Abnormal, Clinically Significant | 0 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: ECG | end of study | Abnormal, Not Clinically Significant | 3 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: ECG | screening | Abnormal, Not Clinically Significant | 4 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: ECG | baseline | Abnormal, Clinically Significant | 0 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: ECG | baseline | Abnormal, Not Clinically Significant | 3 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: ECG | screening | normal | 11 Participants |
Secondary
Phase 2:Maximum Level of Sensory Block
Sensorial block will be verified by bilateral Pinprick test using a 20-G hypodermic needle and will be recorded. Pinprick sensation will be scored as being present (score 1) or absent (score 0). Onset of sensory block is defined as an absent touch sensation (score 0)
Time frame: Intraoperative
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T1 | 0 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T4 | 0 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T8 | 7 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T2 | 0 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T7 | 1 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T5 | 2 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T3 | 0 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T11 | 1 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T10 | 2 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T6 | 4 participants |
| 60 mg Paracetamol 3% (2 mL) | Phase 2:Maximum Level of Sensory Block | T9 | 0 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T6 | 4 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T9 | 2 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T7 | 2 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T8 | 7 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T3 | 0 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T11 | 0 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T4 | 2 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T10 | 0 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T5 | 1 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T2 | 0 participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2:Maximum Level of Sensory Block | T1 | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T10 | 1 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T1 | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T2 | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T3 | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T4 | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T5 | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T6 | 3 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T7 | 1 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T8 | 10 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T9 | 0 participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2:Maximum Level of Sensory Block | T11 | 0 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T6 | 3 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T11 | 0 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T9 | 2 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T5 | 0 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T4 | 1 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T3 | 0 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T10 | 0 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T2 | 0 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T1 | 0 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T8 | 28 participants |
| Phase II Only: Saline Solution 0.9% | Phase 2:Maximum Level of Sensory Block | T7 | 6 participants |
Secondary
Phase 2: Morphine
Phase 2: Total morphine use
Time frame: At 24 and 48 h after anaesthetic IT injection and entire study period, up to 7 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Morphine | first 24 hours | 14.1 mg | Standard Deviation 10.4 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Morphine | entire study period | 24.8 mg | Standard Deviation 19.7 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Morphine | first 48 hours | 24.5 mg | Standard Deviation 19.7 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Morphine | first 24 hours | 12.6 mg | Standard Deviation 4.5 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Morphine | entire study period | 15.8 mg | Standard Deviation 5.1 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Morphine | first 48 hours | 15.8 mg | Standard Deviation 5.1 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Morphine | first 48 hours | 33.5 mg | Standard Deviation 21.5 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Morphine | first 24 hours | 22.8 mg | Standard Deviation 14.7 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Morphine | entire study period | 33.8 mg | Standard Deviation 21.4 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Morphine | first 24 hours | 14.3 mg | Standard Deviation 7.4 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Morphine | entire study period | 21.1 mg | Standard Deviation 13 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Morphine | first 48 hours | 21 mg | Standard Deviation 12.8 |
Secondary
Phase 2: Morphine-related Adverse Events
Percentage of subjects experiencing during the study the morphine-related adverse events pre-specified in the protocol
Time frame: up to 24 hours after surgery, up to 48 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Morphine-related Adverse Events | 1 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Morphine-related Adverse Events | 6 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Morphine-related Adverse Events | 1 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: Morphine-related Adverse Events | 6 Participants |
Secondary
Phase 2: Number of Participants With Need for Supplemental Analgesia
Phase 2: Need for supplementary analgesia, other than the planned morphine PCA
Time frame: Postoperative, up to 48 hours after end of surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Number of Participants With Need for Supplemental Analgesia | 9 Participants |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Number of Participants With Need for Supplemental Analgesia | 11 Participants |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Number of Participants With Need for Supplemental Analgesia | 11 Participants |
| Phase II Only: Saline Solution 0.9% | Phase 2: Number of Participants With Need for Supplemental Analgesia | 10 Participants |
Secondary
Phase 2: SpO2
Oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the blood.
Time frame: at screening, at baseline (before the spinal injection) and at the end of the study (day 6)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: SpO2 | screening | 97.93 Oxygen Saturation percentage | Standard Deviation 0.59 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: SpO2 | end of the study (day 6) | 97.73 Oxygen Saturation percentage | Standard Deviation 1.03 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: SpO2 | baseline | 97.27 Oxygen Saturation percentage | Standard Deviation 1.03 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: SpO2 | screening | 98 Oxygen Saturation percentage | Standard Deviation 0.53 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: SpO2 | end of the study (day 6) | 97.53 Oxygen Saturation percentage | Standard Deviation 0.83 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: SpO2 | baseline | 97.07 Oxygen Saturation percentage | Standard Deviation 1.03 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: SpO2 | baseline | 97.33 Oxygen Saturation percentage | Standard Deviation 1.18 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: SpO2 | screening | 98.27 Oxygen Saturation percentage | Standard Deviation 0.7 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: SpO2 | end of the study (day 6) | 97.8 Oxygen Saturation percentage | Standard Deviation 0.77 |
| Phase II Only: Saline Solution 0.9% | Phase 2: SpO2 | screening | 97.80 Oxygen Saturation percentage | Standard Deviation 0.77 |
| Phase II Only: Saline Solution 0.9% | Phase 2: SpO2 | end of the study (day 6) | 97.6 Oxygen Saturation percentage | Standard Deviation 0.74 |
| Phase II Only: Saline Solution 0.9% | Phase 2: SpO2 | baseline | 96.87 Oxygen Saturation percentage | Standard Deviation 1.36 |
Secondary
Phase 2: Time to First Morphine Use
Phase 2: Time to first morphine use (minutes)
Time frame: Postoperative, up to 48 hours after end of surgery
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Time to First Morphine Use | 351 minutes |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Time to First Morphine Use | 236 minutes |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Time to First Morphine Use | 318 minutes |
| Phase II Only: Saline Solution 0.9% | Phase 2: Time to First Morphine Use | 279 minutes |
Secondary
Phase 2: Time to Readiness for Surgery
Time period from completion of spinal injection (time 0 h) to achievement of sensory and motor block adequate for surgery.
Time frame: Intraoperative
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Time to Readiness for Surgery | 9 minutes |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Time to Readiness for Surgery | 10 minutes |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Time to Readiness for Surgery | 10 minutes |
| Phase II Only: Saline Solution 0.9% | Phase 2: Time to Readiness for Surgery | 8 minutes |
Secondary
Phase 2: Time to Regression of Spinal Block
Time period from spinal injection (time 0 h) to the time when the Bromage score returns to 0 and sensitive perception returns to S1. Bromage scale: I - Free movement of legs and feet II - Just able to flex knees with free movement of feet III - Unable to flex knees, but with free movement of feet IV - Unable to move legs or feet
Time frame: from readiness for surgery,then every 10 min until the maximum level is reached (two consecutive observations with the same level of sensory block) and then every 30 min until regression of spinal block
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Time to Regression of Spinal Block | 285 minutes |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Time to Regression of Spinal Block | 246 minutes |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Time to Regression of Spinal Block | 265 minutes |
| Phase II Only: Saline Solution 0.9% | Phase 2: Time to Regression of Spinal Block | 280 minutes |
Secondary
Phase 2: Time to Sensory Block
Time to maximum level of sensory block
Time frame: Intraoperative
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Time to Sensory Block | 18 minutes |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Time to Sensory Block | 15 minutes |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Time to Sensory Block | 15 minutes |
| Phase II Only: Saline Solution 0.9% | Phase 2: Time to Sensory Block | 17 minutes |
Secondary
Phase 2: Vital Signs
Systolic and Diastolic Blood Pressure (mmHg)
Time frame: at screening, at baseline (before the spinal injection) and at end of the study (Day 6).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Vital Signs | Diastolic Blood Pressure at end of the study (day6) | 79.5 mmHg | Standard Deviation 10.8 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Vital Signs | Diastolic Blood Pressure at screening | 87.1 mmHg | Standard Deviation 11.3 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Vital Signs | systolic Blood Pressure at baseline | 145.5 mmHg | Standard Deviation 13.6 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Vital Signs | systolic Blood Pressure at end of the study (day6) | 130 mmHg | Standard Deviation 14.6 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Vital Signs | Diastolic Blood Pressure at baseline | 83 mmHg | Standard Deviation 8.8 |
| 60 mg Paracetamol 3% (2 mL) | Phase 2: Vital Signs | systolic Blood Pressure at screening | 137 mmHg | Standard Deviation 20.4 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Vital Signs | Diastolic Blood Pressure at baseline | 78.9 mmHg | Standard Deviation 10.3 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Vital Signs | Diastolic Blood Pressure at end of the study (day6) | 78.2 mmHg | Standard Deviation 7.5 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Vital Signs | systolic Blood Pressure at baseline | 146.3 mmHg | Standard Deviation 19.2 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Vital Signs | systolic Blood Pressure at screening | 144.6 mmHg | Standard Deviation 20.5 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Vital Signs | systolic Blood Pressure at end of the study (day6) | 130.3 mmHg | Standard Deviation 11.3 |
| 90 mg Paracetamol 3% (3 mL) | Phase 2: Vital Signs | Diastolic Blood Pressure at screening | 85.7 mmHg | Standard Deviation 7 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Vital Signs | systolic Blood Pressure at screening | 148.5 mmHg | Standard Deviation 14.7 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Vital Signs | systolic Blood Pressure at baseline | 138.7 mmHg | Standard Deviation 10.5 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Vital Signs | Diastolic Blood Pressure at baseline | 77.8 mmHg | Standard Deviation 10 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Vital Signs | Diastolic Blood Pressure at screening | 90.9 mmHg | Standard Deviation 8.2 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Vital Signs | Diastolic Blood Pressure at end of the study (day6) | 79 mmHg | Standard Deviation 6.8 |
| 120 mg Paracetamol 3% (4mL) | Phase 2: Vital Signs | systolic Blood Pressure at end of the study (day6) | 133.5 mmHg | Standard Deviation 10.2 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Vital Signs | Diastolic Blood Pressure at end of the study (day6) | 83.1 mmHg | Standard Deviation 9.3 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Vital Signs | systolic Blood Pressure at screening | 147.7 mmHg | Standard Deviation 15.7 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Vital Signs | systolic Blood Pressure at baseline | 144.8 mmHg | Standard Deviation 12.3 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Vital Signs | systolic Blood Pressure at end of the study (day6) | 138.1 mmHg | Standard Deviation 14.5 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Vital Signs | Diastolic Blood Pressure at screening | 87 mmHg | Standard Deviation 5.1 |
| Phase II Only: Saline Solution 0.9% | Phase 2: Vital Signs | Diastolic Blood Pressure at baseline | 85.9 mmHg | Standard Deviation 5.8 |