NCT05487456

Reduced HPHC Exposure in Cigarette Smokers Switching to P4M3 Gen. 2.0 Compared to Continuing Smoking, or Smoking Abstinence

Completed NA Results posted Last updated 13 March 2024

What this trial tests

NA trial testing P4M3 CA35 in Nicotine in 74 participants. Completed in 7 November 2022.

Timeline

15 July 2022

Primary endpoint
31 August 2022

7 November 2022

Quick facts

Lead sponsor	Philip Morris Products S.A.
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	other
Enrollment	74
Start date	15 July 2022
Primary completion	31 August 2022
Estimated completion	7 November 2022
Sites	1 location across United Kingdom

Drugs / interventions tested

• P4M3 CA35
• P4M3 CM35
• CIG
• Smoking Abstinence

Conditions studied

• Nicotine — all drugs for Nicotine →
• Vaping — all drugs for Vaping →
• Nicotine Vaping — all drugs for Nicotine Vaping →

Sponsor

Philip Morris Products S.A. — full company profile →

Who can join

Adults 21 to 65, any sex, with Nicotine or Vaping. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

3-HPMA Primary · From baseline to 5 days

To measure change in 3-hydroxypropyl mercapturic acid (3-HPMA), which is a biomarker of exposure to Acrolein.

Baseline

Group	Value	95% CI
P4M3 CA35	657.46	469.82 – 920.03
P4M3 CM35	726.84	536.06 – 985.51
Cigarette	703.29	544.68 – 908.10
Smoking Abstinence	724.06	516.52 – 1015.00

After 1 day of exposure

Group	Value	95% CI
P4M3 CA35	154.27	120.24 – 197.92
P4M3 CM35	155.85	131.79 – 184.30
Cigarette	638.77	486.69 – 838.37
Smoking Abstinence	149.66	121.66 – 184.11

After 2 days of exposure

Group	Value	95% CI
P4M3 CA35	171.00	144.04 – 203.00
P4M3 CM35	167.93	141.24 – 199.66
Cigarette	794.49	621.70 – 1015.29
Smoking Abstinence	147.57	119.15 – 182.76

After 3 days of exposure

Group	Value	95% CI
P4M3 CA35	112.48	91.31 – 138.56
P4M3 CM35	109.29	97.88 – 122.02
Cigarette	670.16	496.06 – 905.36
Smoking Abstinence	93.16	82.69 – 104.96

After 4 days of exposure

Group	Value	95% CI
P4M3 CA35	194.46	155.93 – 242.50
P4M3 CM35	241.24	189.75 – 306.70
Cigarette	728.51	549.25 – 966.27
Smoking Abstinence	189.48	154.44 – 232.46

After 5 days of exposure

Group	Value	95% CI
P4M3 CA35	105.20	90.85 – 121.83
P4M3 CM35	111.12	89.54 – 137.90
Cigarette	544.77	373.74 – 794.07
Smoking Abstinence	93.20	81.69 – 106.34

2-CyEMA Primary · From baseline to 5 days

To measure change in 2-cyanoethyl mercapturic acid (2-CyEMA), which is a biomarker of exposure to Acrylonitrile.

Baseline

Group	Value	95% CI
P4M3 CA35	97.17	69.12 – 136.61
P4M3 CM35	108.50	81.79 – 143.92
Cigarette	98.85	77.25 – 126.50
Smoking Abstinence	100.39	70.02 – 143.92

After 1 day of exposure

Group	Value	95% CI
P4M3 CA35	33.47	22.35 – 50.12
P4M3 CM35	37.47	28.39 – 49.44
Cigarette	90.13	69.22 – 117.34
Smoking Abstinence	33.68	22.17 – 51.18

After 2 days of exposure

Group	Value	95% CI
P4M3 CA35	17.99	10.93 – 29.60
P4M3 CM35	22.95	17.71 – 29.75
Cigarette	100.04	77.18 – 129.66
Smoking Abstinence	18.12	10.05 – 32.66

After 3 days of exposure

Group	Value	95% CI
P4M3 CA35	16.40	9.08 – 29.61
P4M3 CM35	20.06	14.91 – 26.98
Cigarette	96.41	71.29 – 130.38
Smoking Abstinence	15.67	8.52 – 28.82

After 4 days of exposure

Group	Value	95% CI
P4M3 CA35	12.79	7.26 – 22.55
P4M3 CM35	16.78	12.70 – 22.19
Cigarette	85.54	61.48 – 119.02
Smoking Abstinence	14.40	8.08 – 25.64

After 5 days of exposure

Group	Value	95% CI
P4M3 CA35	12.31	6.81 – 22.25
P4M3 CM35	17.09	11.93 – 24.47
Cigarette	79.87	54.04 – 118.05
Smoking Abstinence	12.95	7.02 – 23.87

Total NNAL Primary · From baseline to 5 days

To measure change in Total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (total NNAL), which is a biomarker of exposure to 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK).

Baseline

Group	Value	95% CI
P4M3 CA35	114.66	71.39 – 184.15
P4M3 CM35	145.13	96.82 – 217.53
Cigarette	116.41	78.30 – 173.06
Smoking Abstinence	115.95	66.28 – 202.86

After 1 day of exposure

Group	Value	95% CI
P4M3 CA35	58.27	32.64 – 104.03
P4M3 CM35	85.16	58.39 – 124.22
Cigarette	106.12	69.17 – 162.81
Smoking Abstinence	68.39	39.47 – 118.50

After 2 days of exposure

Group	Value	95% CI
P4M3 CA35	46.46	26.01 – 82.96
P4M3 CM35	63.61	40.95 – 98.82
Cigarette	112.97	75.73 – 168.53
Smoking Abstinence	44.14	20.37 – 95.65

After 3 days of exposure

Group	Value	95% CI
P4M3 CA35	42.80	22.50 – 81.41
P4M3 CM35	59.25	36.83 – 95.32
Cigarette	111.82	74.08 – 168.79
Smoking Abstinence	40.39	20.14 – 80.99

After 4 days of exposure

Group	Value	95% CI
P4M3 CA35	36.24	19.60 – 66.99
P4M3 CM35	51.10	32.64 – 80.02
Cigarette	102.41	66.16 – 158.52
Smoking Abstinence	37.82	18.68 – 76.57

After 5 days of exposure

Group	Value	95% CI
P4M3 CA35	32.73	17.63 – 60.78
P4M3 CM35	53.87	32.16 – 90.23
Cigarette	101.05	64.72 – 157.78
Smoking Abstinence	37.94	18.91 – 76.12

COHb Primary · From baseline to 5 days

To measure change in carboxyhemoglobin (COHb), which is a biomarker of exposure to Carbon monoxide (CO).

Baseline

Group	Value	95% CI
P4M3 CA35	2.99	2.53 – 3.53
P4M3 CM35	2.91	2.38 – 3.54
Cigarette	2.58	2.36 – 2.83
Smoking Abstinence	2.71	2.40 – 3.07

After 1 day of exposure

Group	Value	95% CI
P4M3 CA35	3.06	2.60 – 3.60
P4M3 CM35	3.10	2.45 – 3.92
Cigarette	2.69	2.47 – 2.93
Smoking Abstinence	2.96	2.56 – 3.43

After 2 days of exposure

Group	Value	95% CI
P4M3 CA35	1.71	1.58 – 1.86
P4M3 CM35	1.80	1.52 – 2.13
Cigarette	2.87	2.64 – 3.12
Smoking Abstinence	1.64	1.55 – 1.75

After 3 days of exposure

Group	Value	95% CI
P4M3 CA35	1.55	1.43 – 1.68
P4M3 CM35	1.59	1.48 – 1.71
Cigarette	2.80	2.53 – 3.10
Smoking Abstinence	1.57	1.44 – 1.71

After 4 days of exposure

Group	Value	95% CI
P4M3 CA35	1.64	1.39 – 1.95
P4M3 CM35	1.69	1.38 – 2.07
Cigarette	2.72	2.44 – 3.03
Smoking Abstinence	1.45	1.33 – 1.57

After 5 days of exposure

Group	Value	95% CI
P4M3 CA35	1.52	1.41 – 1.63
P4M3 CM35	1.53	1.39 – 1.68
Cigarette	2.78	2.45 – 3.15
Smoking Abstinence	1.45	1.26 – 1.67

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, a total duration for each subject of up to 38 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

P4M3 CA35

Serious: 0/16 (0%)

Deaths: 0/16

P4M3 CM35

Serious: 0/17 (0%)

Deaths: 0/17

Cigarette

Serious: 0/18 (0%)

Deaths: 0/18

Smoking Abstinence

Serious: 0/17 (0%)

Deaths: 0/17

Enrolled But Not Randomized

Serious: 0/6 (0%)

Deaths: 0/6

Other adverse events (12 terms — click to expand)

Reaction	System	P4M3 CA35	P4M3 CM35	Cigarette	Smoking Abstinence	Enrolled But Not Randomized
Headache	Nervous system disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Arthropod Sting	Injury, poisoning and procedural complications	—	—	—	—	—
Skin laceration	Injury, poisoning and procedural complications	—	—	—	—	—
Pain	General disorders	—	—	—	—	—
Dysmenorrhoea	Reproductive system and breast disorders	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—

Data from ClinicalTrials.gov NCT05487456 adverse events section.

Sponsor's own description

To demonstrate the reduction of Biomarkers of Exposure (BoExp) to selected harmful and potentially harmful constituents (HPHC) in smokers switching from cigarette (CIG) to P4M3, an Electronic Nicotine Delivery System (ENDS), compared to continuing cigarette smoking for 5 days.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.